377 Matching Annotations
  1. Last 7 days
    1. c.1441T > C(p.Trp481Arg)

      Case59

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.1441T>C (p.Trp481Arg)

      ClinVar: 189007 https://www.ncbi.nlm.nih.gov/clinvar/variation/189007/

      gnomAD: African 8.031e-5, Overall 2.126e-5 http://gnomad.broadinstitute.org/variant/17-78084529-T-C


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Adult Late Onset Pompe Disease

    2. c.925G > A(p.Gly309Arg)

      Case90

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.925G>A (p.Gly309Arg)

      ClinVar: 188797 https://www.ncbi.nlm.nih.gov/clinvar/variation/188797/

      gnomAD: Ashkenazi Jewish 1.010e-4, Overall 2.860e-5 http://gnomad.broadinstitute.org/variant/17-78081665-G-A


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Adult Late Onset Pompe Disease, 1 other patient has the same genotype

    3. c.2238G > A(p.Trp746*)

      Case69

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.2238G>A (p.Trp746*)

      ClinVar: 370904 https://www.ncbi.nlm.nih.gov/clinvar/variation/370904/

      gnomAD: African 4.011e-5, Overall 1.063e-5 http://gnomad.broadinstitute.org/variant/17-78090815-G-A


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Adult Late Onset Pompe Disease, 1 other patient has the same genotype

    4. c.1548G > A(p.Trp516*)

      Case62

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.1548G>A (p.Trp516*)

      ClinVar: 189025 https://www.ncbi.nlm.nih.gov/clinvar/variation/189025/

      gnomAD: European (Non-Finnish) 1.552e-5, Overall 7.079e-6 http://gnomad.broadinstitute.org/variant/17-78084636-G-A


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Adult Late Onset Pompe Disease, 1 person more with the same genotype

    5. c.1143delC(p.Ala382Leufs*10)

      Case92

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.1143delC (p.Ala382Leufs*10)

      ClinVar: 370263 https://www.ncbi.nlm.nih.gov/clinvar/variation/370263/

      gnomAD: European (Non-Finnish) 8.946e-6, Overall 4.031e-6 http://gnomad.broadinstitute.org/variant/17-78082353-AC-A


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Adult Late Onset Pompe Disease, 1 other patient has the same genotype

    6. c.2242dupG (p.Glu748Glyfs*48)

      Case71

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.2242dupG (p.Glu748Glyfs*48)

      ClinVar: 370651 https://www.ncbi.nlm.nih.gov/clinvar/variation/370651/

      gnomAD: European (Non-Finnish) 1.767e-5, Overall 7.975e-6 http://gnomad.broadinstitute.org/variant/17-78090813-T-TG


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Adult Late Onset Pompe Disease

    7. c.2608C > T(p.Arg870*)

      Case78

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.2608C>T (p.Arg870*)

      ClinVar: 189009 https://www.ncbi.nlm.nih.gov/clinvar/variation/189009/

      gnomAD: European (Non-Finnish) 4.888e-5, Overall 2.662e-5 http://gnomad.broadinstitute.org/variant/17-78092118-C-T


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Adult Late Onset Pompe Disease

    8. c.1796C > A(p.Ser599Tyr)

      Case56

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.1796C>A (p.Ser599Tyr)

      ClinVar: 551558 https://www.ncbi.nlm.nih.gov/clinvar/variation/551558/

      gnomAD: European (Non-Finnish) 2.683e-5, Overall 1.207e-5 http://gnomad.broadinstitute.org/variant/17-78086418-C-A


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Juvenile Late Onset Pompe Disease

    9. c.784G > A(p.Glu262Lys)

      Case85

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.784G>A (p.Glu262Lys)

      ClinVar: 188806 https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

      gnomAD: East Asian 5.016e-5, Overall 1.417e-5 http://gnomad.broadinstitute.org/variant/17-78081447-G-A


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Adult Late Onset Pompe Disease, 2 other patients have the same genotype

    10. c.1143delC(p.Ala382Leufs*10)

      Case58

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.1143delC (p.Ala382Leufs*10)

      CAID: 370263 https://www.ncbi.nlm.nih.gov/clinvar/variation/370263/

      gnomAD: European (Non-Finnish) 8.946e-6, Overall 4.031e-6 http://gnomad.broadinstitute.org/variant/17-78082353-AC-A


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Adult Late Onset Pompe Disease

    1. 20 mg/kg (N = 16)

      Case10HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 0.2 pmol/punch/hr, GAA activity at 33% lower limit of normal

      CaseAddInfo: Late Onset Pompe Disease


      CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1548G>A (p.Trp516Ter)

      ClinVar: 189025 https://www.ncbi.nlm.nih.gov/clinvar/variation/189025/

      gnomAD: European (Non-Finnish) 1.552e-5, Overall 7.079e-6 https://gnomad.broadinstitute.org/variant/17-78084636-G-A


      CaseAddInfo: Patient is compound heterozygous for this variant

    2. 20 mg/kg (N = 16)

      Case22HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 7 mU/U hexosaminidas, GAA activity at 25% lower limit of normal

      CaseAddInfo: Late Onset Pompe Disease


      CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.2608C>T (p.Arg870Ter)

      ClinVar: 189009 https://www.ncbi.nlm.nih.gov/clinvar/variation/189009/

      gnomAD: European (Non-Finnish) 4.888e-5, Overall 2.662e-5 https://gnomad.broadinstitute.org/variant/17-78092118-C-T


      CaseAddInfo: Patient is compound heterozygous for these variants

    3. 10 mg/kg (N = 3)

      Case6HPOsFreeText: 10 mg/kg GAA treatment, GAA activity at 1 pmol/punch/hr, GAA activity at 10% lower limit of normal

      CaseAddInfo: Late Onset Pompe Disease


      CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.2242dupG (p.Glu748Glyfs)

      ClinVar: 370651 https://www.ncbi.nlm.nih.gov/clinvar/variation/370651/

      gnomAD: European (Non-Finnish) 1.767e-5, Overall 7.975e-6 https://gnomad.broadinstitute.org/variant/17-78090813-T-TG


      CaseAddInfo:

    4. 20 mg/kg (N = 16)

      Case20HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 9 pmol/spot/hr, GAA activity at 18% lower limit of normal

      CaseAddInfo: Late Onset Pompe Disease


      CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.2459_2461delCTG (p.Ala820del)

      ClinVar: 456404 https://www.ncbi.nlm.nih.gov/clinvar/variation/456404/

      gnomAD: European (Non-Finnish) 6.492e-5, Overall 3.190e-5 https://gnomad.broadinstitute.org/variant/17-78091524-GGCT-G


      CaseAddInfo:

    5. 10 mg/kg (N = 3)

      Case4HPOsFreeText: 10 mg/kg GAA treatment, GAA activity at 0.1 pmol/punch/hr, GAA activity at 33% lower limit of normal

      CaseAddInfo: Late Onset Pompe Disease


      CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1441T>C (p.Trp481Arg)

      ClinVar: 189007 https://www.ncbi.nlm.nih.gov/clinvar/variation/189007/

      gnomAD: African 8.031e-5, Overall 2.126e-5 https://gnomad.broadinstitute.org/variant/17-78084529-T-C


      CaseAddInfo:

    6. 20 mg/kg (N = 16)

      Case17HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 0.38 umol/g/h, GAA activity at 12.7% lower limit of normal

      CaseAddInfo: Late Onset Pompe Disease


      CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.2242dupG (p.Glu748Glyfs)

      ClinVar: 370651 https://www.ncbi.nlm.nih.gov/clinvar/variation/370651/

      gnomAD: European (Non-Finnish) 1.767e-5, Overall 7.975e-6 https://gnomad.broadinstitute.org/variant/17-78090813-T-TG


      CaseAddInfo:

    7. 20 mg/kg (N = 16)

      Case8HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 8 pmol/punch/hr, GAA activity at 33% lower limit of normal

      CaseAddInfo: Late Onset Pompe Disease


      CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.2242dupG (p.Glu748Glyfs)

      ClinVar: 370651 https://www.ncbi.nlm.nih.gov/clinvar/variation/370651/

      gnomAD: European (Non-Finnish) 1.767e-5, Overall 7.975e-6 https://gnomad.broadinstitute.org/variant/17-78090813-T-TG


      CaseAddInfo:

    8. 20 mg/kg (N = 16)

      Case14HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 0.1 umol/h/L, GAA activity at 33% lower limit of normal

      CaseAddInfo: Late Onset Pompe Disease


      CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 https://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1441T>C (p.Trp481Arg)

      ClinVar: 189007 https://www.ncbi.nlm.nih.gov/clinvar/variation/189007/

      gnomAD: African 8.031e-5, Overall 2.126e-5 https://gnomad.broadinstitute.org/variant/17-78084529-T-C


      CaseAddInfo:

    1. 2

      CaseVI,2: Adult onset, 61 years diagnosis

      CasePresentingHPOs: HP:0003701, HP:0002795, HP:0003388, HP:0003236, HP:0003198 (Proximal muscle weakness, Abnormal respiration, Easy fatiguability, Increased serum CK, Myopathy)

      HPOsFreeText: GAA activity from dried blood spot: 0.22%, Forced Vital Capacity Seated: 2040 (46%), 6-Minute Walking Test: 418 min, Plasma CK 2.5-5x Normal

      CaseAddInfo: Late-Onset Pompe Disease

    2. 1

      CaseVI,1: Early adult onset, 63 years diagnosis

      CasePresentingHPOs: HP:0003701, HP:0003327, HP:0002795, HP:0003388, HP:0003326 (Proximal muscle weakness, Axial muscle weakness, Abnormal respiration, Easy fatiguability, Myalgia)

      HPOsFreeText: GAA activity from dried blood spot: 0.24%, Forced Vital Capacity Seated: 1520 (38%)

      CaseNotHPOs: HP:0003236 (Increased serum CK)

      CaseAddInfo: Late-Onset Pompe Disease

    3. VII

      CaseVII: Adolescent onset, 33 years diagnosis

      CasePresentingHPOs: HP:0003701, HP:0003236, HP:0002460, HP:0003394 (Proximal muscle weakness, Increased serum CK, Distal muscle weakness, Muscle cramps)

      HPOsFreeText: GAA activity from dried blood spot: 0.20%, Forced Vital Capacity Seated: 5260 (112%), Plasma CK 2.5-5x Normal, Vacuoles in histology

      CaseNotHPOs: HP:0002795 (Abnormal respiration)

      CaseAddInfo: Late-Onset Pompe Disease

    4. VIII

      CaseVIII: Early adult onset, 56 years diagnosis

      CasePresentingHPOs: HP:0003701, HP:0003236, HP:0003388, HP:0003326, HP:0003198 (Proximal muscle weakness, Increased serum CK, Easy fatiguability, Myalgia, Myopathy)

      HPOsFreeText: GAA activity from dried blood spot: 0.13%, Forced Vital Capacity Seated: 2480 (75%), Plasma CK 2.5-5x Normal, 6-Minute Walking Test: 385 min

      CaseNotHPOs: HP:0002795 (Abnormal respiration)

      CaseAddInfo: Late-Onset Pompe Disease, Reduced staining for dystrophin in patient VIII suggested Becker dystrophy before LOPD diagnosis

    1. LOPD-16

      CaseLOPD-16: 2.5 weeks diagnosis

      HPOsFreeText: GAA activity 2.5 (nmol · h−1 · mg−1), Mean percentage of normal 3.6%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.2065G>A (p.Glu689Lys)

      ClinVar: 4030 https://www.ncbi.nlm.nih.gov/clinvar/variation/4030/

      gnomAD: East Asian 0.2355, Overall 0.05524 http://gnomad.broadinstitute.org/variant/17-78087041-G-A


      Multiple interpretations of p.W746C possible, below is considered the most likely

      Variant3: NM_000152.4:c.2238G>C (p.Trp746Cys)

      ClinVar: 265160 https://www.ncbi.nlm.nih.gov/clinvar/variation/265160/

      gnomAD: European (Non-Finnish) 5.673e-4, Overall 3.083e-4 http://gnomad.broadinstitute.org/variant/17-78090815-G-C


      CaseAddInfo: Late Onset Pompe Disease, Nomenclature claims Variant 2 and 3 are in cis

    2. LOPD-17

      CaseLOPD-17: 6 weeks diagnosis

      HPOsFreeText: GAA activity 6.5 (nmol · h−1 · mg−1), Mean percentage of normal 9.2%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1552-3C>G

      ClinVar: 419722 https://www.ncbi.nlm.nih.gov/clinvar/variation/419722/

      gnomAD: European (Non-Finnish) 2.713e-4, Overall 1.344e-4 http://gnomad.broadinstitute.org/variant/17-78084737-C-G


      CaseAddInfo: Late Onset Pompe Disease

    3. LOPD-19

      CaseLOPD-19: 2 weeks diagnosis

      HPOsFreeText: GAA activity 2.7 (nmol · h−1 · mg−1), Mean percentage of normal 3.8%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1115A>T (p.His372Leu)

      ClinVar: 370483 https://www.ncbi.nlm.nih.gov/clinvar/variation/370483/

      gnomAD: Not in gnomAD


      CaseAddInfo: Late Onset Pompe Disease

    4. LOPD-18

      CaseLOPD-18: 2 weeks diagnosis

      HPOsFreeText: GAA activity 2.9 (nmol · h−1 · mg−1), Mean percentage of normal 4.0%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.2188G>T (p.Glu730Ter)

      ClinVar: 495665 https://www.ncbi.nlm.nih.gov/clinvar/variation/495665/

      gnomAD: Not in gnomAD


      CaseAddInfo: Late Onset Pompe Disease

    5. LOPD-14

      CaseLOPD-14: 2 weeks diagnosis

      HPOsFreeText: GAA activity 3.0 (nmol · h−1 · mg−1), Mean percentage of normal 4.2%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.2509C>T (p.Arg837Cys)

      ClinVar: 456408 https://www.ncbi.nlm.nih.gov/clinvar/variation/456408/

      gnomAD: European (Non-Finnish) 4.676e-5, Overall 2.487e-5 http://gnomad.broadinstitute.org/variant/17-78092019-C-T


      CaseAddInfo: Late Onset Pompe Disease

    1. 7

      Case7: Female, 37 years onset, 38 years diagnosis, Italy

      HPOsFreeText: See Group Phenotypes, ERT started at 40, GAA Activity at ~4.5 pmol/min/mg before ERT and ~5.5 after

      GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.2237G>A (p.Trp746Ter)

      ClinVar: 280063 https://www.ncbi.nlm.nih.gov/clinvar/variation/280063/

      gnomAD: European (Non-Finnish) 8.834e-6, Overall 3.988e-6 http://gnomad.broadinstitute.org/variant/17-78090814-G-A


      CaseAddInfo: Late Onset Pompe Disease

    2. 15

      Case15: Female, 39 years onset, 40 years diagnosis, Italy

      HPOsFreeText: See Group Phenotypes, ERT started at 41, GAA Activity at ~6.5 pmol/min/mg before ERT and ~11 after

      GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.2237G>A (p.Trp746Ter)

      ClinVar: 280063 https://www.ncbi.nlm.nih.gov/clinvar/variation/280063/

      gnomAD: European (Non-Finnish) 8.834e-6, Overall 3.988e-6 http://gnomad.broadinstitute.org/variant/17-78090814-G-A


      CaseAddInfo: Late Onset Pompe Disease

    1. 16

      Case#: Patient 16, female

      CasePresentingHPOs: HP:0003325

      CaseAddInfo: onset and diagnosis at 32yo

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NC_000017.11:g.(?80118193)(80118357_?)del

      ClinVar: 456368, https://www.ncbi.nlm.nih.gov/clinvar/variation/456368/

      gnomAD: n/a

    2. 12

      Case#: Patient 12, male

      CasePresentingHPOs: HP:0003236

      CaseAddInfo: 42yo at onset, 46yo at diagnosis

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NM_000152.4(GAA):c.1438-2A>G

      ClinVar: 526521, https://www.ncbi.nlm.nih.gov/clinvar/variation/526521/

      gnomAD: n/a

    3. 3

      Case#: Patient 3, female

      CasePresentingHPOs: HP:0003236

      CaseAddInfo: 29yo at onset, 39yo at diagnosis

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NM_000152.4(GAA):c.784G>A (p.Glu262Lys)

      ClinVar: 188806, https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

      gnomAD: 1.66e-05, http://exac.broadinstitute.org/variant/17-78081447-G-A

    4. 17

      Case#: Patient 17, female

      CasePresentingHPOs: HP:0003236

      CaseAddInfo: 38yo at onset, 39yo at diagnosis

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NM_000152.4(GAA):c.2237G>A (p.Trp746Ter)

      ClinVar: 280063, https://www.ncbi.nlm.nih.gov/clinvar/variation/280063/

      gnomAD: 8.301e-06, http://exac.broadinstitute.org/variant/17-78090814-G-A

    5. 8

      Case#: Patient 8, male

      CasePresentingHPOs: HP:0003236, HP:0003325

      CaseAddInfo: 30yo at onset, 35yo at diagnosis

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NC_000017.11:g.(?80118193)(80118357_?)del

      ClinVar: 456368, https://www.ncbi.nlm.nih.gov/clinvar/variation/456368/

      gnomAD: n/a

    6. 11

      Case#: Patient 11, male

      CasePresentingHPOs: HP:0003236, HP:0003325

      CaseAddInfo: 24yo at onset, 47yo at diagnosis

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NC_000017.11:g.(?80118193)(80118357_?)del

      ClinVar: 456368, https://www.ncbi.nlm.nih.gov/clinvar/variation/456368/

      gnomAD: n/a

    1. 7

      Patient7: female, Serbian

      CasePresentingHPOs: HP:0003677, HP:0003236, HP:0003325

      HPOsFreeText: CK < 10x increase

      CaseNotHPOs: HP:0002093

      CaseAddInfo: onset in middle age

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant 1: NM_000152.4(GAA):c.2269C>T (p.Gln757Ter)

      ClinVar: 429727, https://www.ncbi.nlm.nih.gov/clinvar/variation/429727/

      gnomAD: n/a

      Variant2: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

    2. 3

      Patient3: male, German

      CasePresentingHPOs: HP:0003677, HP:0003236, HP:0003325, HP:0003327

      HPOsFreeText: CK < 10x increase , CK = 1729 U/L, reduced alpha-glucosidase activity, treated with ERT

      CaseNotHPOs: HP:0002093, HP:0003457

      CaseAddInfo: onset after 30yo, previously diagnosed with Brugada Syndrome, but Pompe was confirmed via Sanger Sequencing. Asymptomatic brother also diagnosed with Pompe.

      CasePreviousTesting: same as group, EMG

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.2331+2T>A

      ClinVar: 371281, https://www.ncbi.nlm.nih.gov/clinvar/variation/371281/

      gnomAD: n/a

      Variant2: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

    1. Case35: Male, 26 years report

      HPOsFreeText: ERT not started, 6 Minute Walking Test at 645 meters, Forced Vital Capacity at 101%

      GenotypingMethod: GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.655G>A (p.Gly219Arg)

      ClinVar: 189065 https://www.ncbi.nlm.nih.gov/clinvar/variation/189065/

      gnomAD: African 4.024e-5, Overall 1.809e-5 http://gnomad.broadinstitute.org/variant/17-78079656-G-A


      CaseAddInfo: Late Onset Pompe Disease

    2. Case12: Male, 45 years report

      HPOsFreeText: 5 years of ERT completed, 6 Minute Walking Test at 301 meters, Forced Vital Capacity at 13%

      GenotypingMethod: GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.655G>A (p.Gly219Arg)

      ClinVar: 189065 https://www.ncbi.nlm.nih.gov/clinvar/variation/189065/

      gnomAD: African 4.024e-5, Overall 1.809e-5 http://gnomad.broadinstitute.org/variant/17-78079656-G-A


      CaseAddInfo: Late Onset Pompe Disease

    3. Case17: Female, 49 years report

      HPOsFreeText: 2 years of ERT completed, 6 Minute Walking Test at 314 meters, Forced Vital Capacity at 54%

      GenotypingMethod: GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1548G>A (p.Trp516Ter)

      ClinVar: 189025 https://www.ncbi.nlm.nih.gov/clinvar/variation/189025/

      gnomAD: European (Non-Finnish) 1.552e-5, Overall 7.079e-6 http://gnomad.broadinstitute.org/variant/17-78084636-G-A


      CaseAddInfo: Late Onset Pompe Disease

    4. Case26: Female, 65 years report

      HPOsFreeText: 5 years of ERT completed, Forced Vital Capacity at 57%

      GenotypingMethod: GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1548G>A (p.Trp516Ter)

      ClinVar: 189025 https://www.ncbi.nlm.nih.gov/clinvar/variation/189025/

      gnomAD: European (Non-Finnish) 1.552e-5, Overall 7.079e-6 http://gnomad.broadinstitute.org/variant/17-78084636-G-A


      CaseAddInfo: Late Onset Pompe Disease

    5. Case27: Male, 71 years report

      HPOsFreeText: 0.3 years of ERT completed, 6 Minute Walking Test at 348 meters, Forced Vital Capacity at 53%

      GenotypingMethod: GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.2608C>T (p.Arg870Ter)

      ClinVar: 189009 https://www.ncbi.nlm.nih.gov/clinvar/variation/189009/

      gnomAD: European (Non-Finnish) 4.888e-5, Overall 2.662e-5 http://gnomad.broadinstitute.org/variant/17-78092118-C-T


      CaseAddInfo: Late Onset Pompe Disease

    6. Case23: Male, 77 years report

      HPOsFreeText: 2 years of ERT completed, 6 Minute Walking Test at 120 meters, Forced Vital Capacity at 40%

      GenotypingMethod: GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.925G>A (p.Gly309Arg)

      ClinVar: 188797 https://www.ncbi.nlm.nih.gov/clinvar/variation/188797/

      gnomAD: Ashkenazi Jewish 1.010e-4, Overall 2.860e-5 http://gnomad.broadinstitute.org/variant/17-78081665-G-A


      CaseAddInfo: Late Onset Pompe Disease

    1. 7

      Family 7 - Patient 7

      FamilyPresentingHPOs: HP:0007340, HP:0003701, HP:0003306, HP:0002111, HP:0040081

      HPOsFreeText: muscle pathology with vacuolar myopathy with glycogen excess, myopathic muscle unit action potentials

      FamilyNotHPOs: HP:0010628, HP:0002015, HP:0003691, HP:0002650

      Ethnicity: Iranian

      ProbandLabel:

      FamilyAddInfo: male, 20yo at onset, 23yo at diagnosis, MRC sum score = 96, patient required use of NIV

      FamilyPreviousTesting: Respiratory Evaluation: FVC = 20%, CK = 2,550 U/L, muscle pathology examined, DBS enzyme activity (with inhibition) = 0.1 μmol/L/h, NCS, EMG

      FamilyGenotypingMethod: GAA analyzed with Sanger Sequencing for entire coding region and conserved exon-intron splice junctions, PCR performed for deletion screening

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NM_000152.4(GAA):c.2662G>T (p.Glu888Ter)

      ClinVar: 578595, https://www.ncbi.nlm.nih.gov/clinvar/variation/578595/

      gnomAD: 1.65e-05, http://exac.broadinstitute.org/variant/17-78092467-G-T

    2. 8a

      Family 8 - Patients 8a and 8b

      FamilyPresentingHPOs: HP:0007340, HP:0003701, HP:0000467, HP:0003327, HP:0010628, HP:0002015, HP:0003691, HP:0002650, HP:0040081

      HPOsFreeText: 8b muscle pathology with mild lysosomal vacuolar myopathy with slight glycogen excess, no metachromatic debris, myopathic muscle unit action potentials

      FamilyNotHPOs: HP:0003306

      Ethnicity: Iranian

      ProbandLabel: 8a, female, 27yo at onset, 32yo at diagnosis

      FamilyAddInfo: 8b (male) dx at 40yo, 8a MRC sum score = 82, 8b MRC sum score = 60, 8b is wheelchair bound, both patients required use of NIV

      FamilyPreviousTesting: Respiratory Evaluation: 8a FVC = 102%, 8b FVC = 17%, 8a CK = 268 U/L, 8b CK = 199 U/L, muscle pathology (examined only in 8b), DBS enzyme activity (with inhibition) for 8a = 0.11 μmol/L/h, for 8b = 0.15 μmol/L/h, NCS, EMG

      FamilyGenotypingMethod: GAA analyzed with Sanger Sequencing for entire coding region and conserved exon-intron splice junctions, PCR performed for deletion screening

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NM_000152.4(GAA):c.2078dupA (p.Ala694Glyfs)

      ClinVar: 180143, https://www.ncbi.nlm.nih.gov/clinvar/variation/180143/

      gnomAD: n/a

    3. 3

      Family 3 - Patient 3

      FamilyPresentingHPOs: HP:0002355, HP:0003701, HP:0000467, HP:0003327, HP:0002111, HP:0040081, HP:0100284

      HPOsFreeText: Vacuolar myopathy, myopathic muscle unit action potentials

      FamilyNotHPOs: HP:0010628, HP:0002015, HP:0003691, HP:0003306, HP:0002650

      NotHPOsFreeText:

      Ethnicity: Iranian

      ProbandLabel:

      FamilyAddInfo: female, 2yo at onset, 26yo at diagnosis, MRC sum score = 76, NIV used beginning at 22yo

      FamilyPreviousTesting: Respiratory Evaluation: FVC = 31%, CK = 1,551 U/L, Vacuolar myopathy present in muscle pathology exam, DBS enzyme activity (with inhibition) = 5.1 μmol/L/h, NCS, EMG

      FamilyGenotypingMethod: GAA analyzed with Sanger Sequencing for entire coding region and conserved exon-intron splice junctions, PCR performed for deletion screening

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NM_000152.4(GAA):c.1004G>A (p.Gly335Glu)

      ClinVar: 180142, https://www.ncbi.nlm.nih.gov/clinvar/variation/180142/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

    4. 9

      Family 9 - Patient 9

      FamilyPresentingHPOs: HP:0007340, HP:0003701, HP:0000467, HP:0003327, HP:0010628, HP:0003306, HP:0002111, HP:0040081

      HPOsFreeText: muscle pathology with slight vacuolar myopathy with mild glycogen excess

      FamilyNotHPOs: HP:0002015, HP:0003691, HP:0002650

      Ethnicity: Iranian

      ProbandLabel:

      FamilyAddInfo: onset at 28yo, diagnosed at 35yo, MRC sum score = 81

      FamilyPreviousTesting: Respiratory Evaluation: FVC = 71%, CK = 748 U/L, muscle pathology examined, DBS enzyme activity (with inhibition) = 3.5 μmol/L/h

      FamilyGenotypingMethod: GAA analyzed with Sanger Sequencing for entire coding region and conserved exon-intron splice junctions, PCR performed for deletion screening

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NM_000152.4(GAA):c.1799G>A (p.Arg600His)

      ClinVar: 370130, https://www.ncbi.nlm.nih.gov/clinvar/variation/370130/

      gnomAD: 8.675e-06, http://exac.broadinstitute.org/variant/17-78086421-G-A

    1. P15

      Patient15: Female, 56yo

      CasePresentingHPOs: HP:0003077, HP:0000822

      HPOsFreeText: LOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 19yr disease duration, ERT lasted 48mo

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NC_000017.11:g.(?80118193)(80118357_?)del (c.2481 + 102_2646 + 31del)

      ClinVar: 456368, https://www.ncbi.nlm.nih.gov/clinvar/variation/456368/

      gnomAD: n/a

    2. P14

      Patient14: Female, 54yo

      CasePresentingHPOs: HP:0003077, HP:0000822

      HPOsFreeText: LOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 18yr disease duration, ERT lasted 44mo

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NC_000017.11:g.(?80118193)(80118357_?)del (c.2481 + 102_2646 + 31del)

      ClinVar: 456368, https://www.ncbi.nlm.nih.gov/clinvar/variation/456368/

      gnomAD: n/a

    3. P19

      Patient19: Female, 61yo

      CasePresentingHPOs: HP:0000822

      HPOsFreeText: LOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 2yr disease duration, ERT lasted 9mo

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.925G>A (p.Gly309Arg)

      ClinVar: 188797, https://www.ncbi.nlm.nih.gov/clinvar/variation/188797/

      gnomAD: 0.00002860, http://gnomad.broadinstitute.org/variant/17-78081665-G-A

    4. P8a

      Patient8: Female, 61yo

      CasePresentingHPOs: HP:0000822, HP:0003077

      HPOsFreeText: LOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 5yr follow-up MRI, 21yr disease duration, ERT lasted for 63mo

      CasePMIDs: PMID: 25614309

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.1478C>T (p.Pro493Leu)

      ClinVar: 379593, https://www.ncbi.nlm.nih.gov/clinvar/variation/379593/

      gnomAD: 0.00001416, http://gnomad.broadinstitute.org/variant/17-78084566-C-T

    5. P5a

      Patient5: Male, 52yo

      CasePresentingHPOs: HP:0003077, HP:0000822

      HPOsFreeText: LOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 15yr disease duration, ERT lasted for 63mo, 5yr follow-up MRI

      CasePMIDs: PMID: 25614309

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.1478C>T (p.Pro493Leu)

      ClinVar: 379593, https://www.ncbi.nlm.nih.gov/clinvar/variation/379593/

      gnomAD: 0.00001416, http://gnomad.broadinstitute.org/variant/17-78084566-C-T

    6. P17

      Patient17: Male, 81yo

      CasePresentingHPOs: HP:0003077, HP:0000822

      HPOsFreeText: LOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 6yr disease duration, ERT lasted 37mo

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.925G>A (p.Gly309Arg)

      ClinVar: 188797, https://www.ncbi.nlm.nih.gov/clinvar/variation/188797/

      gnomAD: 0.00002860, http://gnomad.broadinstitute.org/variant/17-78081665-G-A

    7. P9

      Patient9: Male, 64yo

      CasePresentingHPOs: HP:0000822, HP:0000819, HP:0001513

      HPOsFreeText: LOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 11yr disease duration, ERT lasted 14mo

      CasePMIDs: PMID: 25614309

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.925G>A (p.Gly309Arg)

      ClinVar: 188797, https://www.ncbi.nlm.nih.gov/clinvar/variation/188797/

      gnomAD: 0.00002860, http://gnomad.broadinstitute.org/variant/17-78081665-G-A

    8. P10a

      Patient10: Female, 75yo

      CasePresentingHPOs: HP:0000822

      HPOsFreeText: LOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 5yr follow-up MRI, 40yr disease duration, ERT lasted 103mo

      CasePMIDs: PMID: 25614309

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NC_000017.11:g.(?80118193)(80118357_?)del (del exon 18)

      ClinVar: 456368, https://www.ncbi.nlm.nih.gov/clinvar/variation/456368/

      gnomAD: n/a

    1. A 50-year-old man

      Subject II-8: male, 50yo

      CasePresentingHPOs: HP:0002094, HP:0002015, HP:0003323, HP:0002878, HP:0006532, HP:0000822, HP:0005978, HP:0003119, HP:0004325, HP:0009055, HP:0012533, HP:0002540, HP:0003698, HP:0030829, HP:0003236, HP:0010899, HP:0003445, HP:0001271

      HPOsFreeText: Previously hospitalized 3 times, during the last of which he received a tracheostomy and was dependent on a ventilator. When study began, he was being treated with IV gamma-globulin therapy for likely chronic inflammatory demyelinating polyneuropathy. Motor examination showed symmetrical 2/5 proximal and 4/5 distal strength. Absent reflexes of bilateral biceps, triceps, patellar, and ankle jerk. Allodynia in soles and distal parts of both legs, normal cardiologic examination, bilateral reduced breath sounds, CK = 132 IU/L, aspartate aminotransferase = 46 IU/L, denervation and spontaneous activity with complex repetitive discharges on muscles associated with cranial nerves and cervical, thoracic, and lumbar areas. Demyelinating, mixed sensorimotor polyneuropathy with absent F wave, reduced GAA activity. 6mo after discharge with tracheostomy and ventilator support patient died from respiratory failure due to pulmonary infection.

      CaseNotHPOs: HP:0007185, HP:0001291, HP:0003487, HP:0002370, HP:0011675

      NotHPOsFreeText: Absent Hoffmann signs, no myotonic phenomenon

      CaseAddInfo: Symptoms (dyspnea, dysphagia, and muscle weakness) had been occurring for 2yrs prior to initiation of case study. based on pedigree, it is likely this patients variants are in trans

      CasePMIDs:

      CasePreviousTesting: neurological examination, motor examination, cardiologic eamination, pulmonary evaluation, lab studies (CK, AST), ECG, needle electromyogram, nerve conduction studies, DBS

      CaseGenotypingMethod: genetic analysis (method not described)

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.2560C>T (p.Arg854Ter)

      ClinVar: 4034, https://www.ncbi.nlm.nih.gov/clinvar/variation/4034/

      gnomAD: 0.0002090, http://gnomad.broadinstitute.org/variant/17-78092070-C-T

      Variant3: NM_000152.4(GAA):c.1551+42G>A

      ClinVar: 496841, https://www.ncbi.nlm.nih.gov/clinvar/variation/496841/

      gnomAD: 0.003009, http://gnomad.broadinstitute.org/variant/17-78084681-G-A

    1. 2/M

      Patient2: Male, African American, 11yo

      CasePresentingHPOs:

      HPOsFreeText: IOPD, rhGAA IgG antibody titer = 800, CRIM positive

      CaseNotHPOs:

      NotHPOsFreeText: no infusion associated reactions

      CaseAddInfo: 15mo at diagnosis, 16mo at ERT start

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.1447G>A (p.Gly483Arg)

      ClinVar: 285157, https://www.ncbi.nlm.nih.gov/clinvar/variation/285157/

    1. Detailed characteristics of these patients

      Patient6: male, 50yo, adult onset

      CasePresentingHPOs:

      HPOsFreeText: LOPD, BMI = 26.3 / 26.6 / n-a, required use of wheelchair and BiPAP, WGMS = 3 / 4 / n-a

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.1143delC (p.Ala382Leufs)

      ClinVar: 370263, https://www.ncbi.nlm.nih.gov/clinvar/variation/370263/

      gnomAD: 0.000004031, http://gnomad.broadinstitute.org/variant/17-78082353-AC-A

    2. Detailed characteristics of these patients

      Patient13: male, 32yo, juvenile onset

      CasePresentingHPOs:

      HPOsFreeText: LOPD, BMI = 24.9 / 25 / n-a, WGMS = 3 / 3 / n-a

      CaseNotHPOs: HP:0002355

      NotHPOsFreeText: did not require respiratory support

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NC_000017.11:g.(?80118193)(80118357_?)del (c.2481+102_2646+31del)

      ClinVar: 456368, https://www.ncbi.nlm.nih.gov/clinvar/variation/456368/

      gnomAD: n/a

    1. 10a

      Patient10: Male, 45yo at diagnosis, 58yo at ERT

      CasePresentingHPOs:

      HPOsFreeText: anti rh-GAA antibodies titre = 1:3200, enzyme (μmol/g/h) = 0.39 (3-20), mobility aid required before and after ERT

      CaseNotHPOs:

      NotHPOsFreeText: NIV not required

      CaseAddInfo: 27yr disease duration, patient discontinued ERT, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.258dupC (p.Asn87Glnfs)

      ClinVar: 282842, https://www.ncbi.nlm.nih.gov/clinvar/variation/282842/

      gnomAD: 2.653e-05, http://exac.broadinstitute.org/variant/17-78078636-T-TC

    2. 20

      Patient20: Female, 46yo at diagnosis and ERT

      CasePresentingHPOs:

      HPOsFreeText: anti rh-GAA antibodies titre = 1:12,800, enzyme (μmol/g/h) = 0.64 (3-20), NIV required before and after ERT

      CaseNotHPOs:

      NotHPOsFreeText: mobility aid not required

      CaseAddInfo: 26yr disease progression, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.2242dupG (p.Glu748Glyfs)

      ClinVar: 370651, https://www.ncbi.nlm.nih.gov/clinvar/variation/370651/

      gnomAD: 1.66e-05, http://exac.broadinstitute.org/variant/17-78090813-T-TG

    3. 19

      Patient19: Male, 54yo at diagnosis and ERT

      CasePresentingHPOs:

      HPOsFreeText: anti rh-GAA antibodies titre = 1:6400, enzyme (μmol/g/h) = 0.41 (3-20), NIV and mobility aid required before and after ERT

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 35yr disease duration, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.2242dupG (p.Glu748Glyfs)

      ClinVar: 370651, https://www.ncbi.nlm.nih.gov/clinvar/variation/370651/

      gnomAD: 1.66e-05, http://exac.broadinstitute.org/variant/17-78090813-T-TG

    4. 21

      Patient21: Male, 56yo at diagnosis and ERT

      CasePresentingHPOs:

      HPOsFreeText: anti rh-GAA antibodies titre = 1:1600, enzyme (μmol/g/h) = 0.57 (2-10), NIV and mobility aid required before and after ERT, developed wheelchair dependence after ERT

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 35yr disease duration, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.1128_1129delGGinsC (p.Trp376Cysfs)

      ClinVar: 189041, https://www.ncbi.nlm.nih.gov/clinvar/variation/189041/

      gnomAD: n/a

    5. 22a

      Patient22: Female, 40yo at diagnosis and ERT

      CasePresentingHPOs:

      HPOsFreeText: anti rh-GAA antibodies titre = 1:12,800, enzyme = 2.77 pmol/punch/h (7.3–39), NIV and mobility aid required before and after ERT

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 18yr disease duration, patient discontinued ERT, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.258dupC (p.Asn87Glnfs)

      ClinVar: 282842, https://www.ncbi.nlm.nih.gov/clinvar/variation/282842/

      gnomAD: 2.653e-05, http://exac.broadinstitute.org/variant/17-78078636-T-TC

    6. 17

      Patient17: Male, 34yo at diagnosis and ERT

      CasePresentingHPOs:

      HPOsFreeText: anti rh-GAA antibodies titre = 1:800, enzyme (μmol/g/h) = 0.75 (3-20), NIV required only after ERT began

      CaseNotHPOs:

      NotHPOsFreeText: mobility aid not required

      CaseAddInfo: 17yr disease duration, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_001079803.2(GAA):c.896T>C (p.Leu299Pro)

      ClinVar: 180144, https://www.ncbi.nlm.nih.gov/clinvar/variation/180144/

      gnomAD: n/a

    1. Patient 3

      Case3: Female, Caucasian, United States, 8 days diagnosis, 2 weeks onset, 1.2 years report

      CasePresentingHPOs: HP:0003236, HP:0002194, HP:0003749, HP:0003093, HP:0003273, HP:0003184, HP:0008796, HP:0006380, HP:0001435, HP:0003484, HP:0006589, HP:0003725, HP:0008981, HP:0001270, HP:0001290, HP:0002376 (Increased serum CK, Delayed gross motor development, Pelvic girdle muscle weakness, Limited hip extension, Hip flexion contractures, Decreased hip abduction, Externally rotated hips, Knee flexion contracture, Abnormality of the shoulder girdle musculature, Upper limb muscle weakness, Flaring of lower rib cage, Firm muscles, Calf muscle hypertrophy, Motor delay, Generalized hypotonia, Developmental regression)

      HPOsFreeText: Had hyperCKemia since the second week of life (605 IU/L, day 8 of life; 513 IU/L, age 3 months), At 5 months she was unable to hold head up to 90 degrees in prone, unable to sit with slight support but unable to prop-sit, and unable to bear weight on hands in prone with AIMS score at the 10th percentile, PT evaluation at age 6 months revealed progression of delay in gross motor milestones, with AIMS score at the 3rd percentile, Unable to sit upright or unsupported and unable to push up on arms in prone, scored only 20% on Dimension B (Sitting) of the GMFM, Imbalanced weakness was evident in trunk and pelvic musculature with predominant active use of, and positioning in, hip flexion/abduction/external rotation in supine, prone and sitting, decreased use of hip extensors and abdominals, and limitation in the use of abdominal obliques for active trunk rotation, Adduction, Tightness in hip flexors, IT bands, and plantar flexors present, Weakness in abdominals, and in hip extension, ankle dorsiflexion, and ankle eversion persisted at 16 months after walking began, ALT 198 U/L (Normal 5–40 U/L), AST 139 U/L (Normal 15–41 U/L), ALP 248 U/L (Normal 24–170 U/L), Urinary Glc4 7.3 mmol/mol creatinine (Normal ≤8.3 mmol/mol creatinine)

    1. 6

      Case6: Male, 1 yr onset, 2 yr diagnosis, 8.2 yr report

      CasePresentingHPOs: HP:0001371 (Contractures)

      HPOsFreeText: Wheelchair partially used, FVC z-score sitting -3.47 (59% pred), FVC z-score supine -4.36 (48% pred), 79% MRC Scale, 3078 CK U/l, 4.5 GAA activity (nmol/h/mg)^h from cultured fibroblasts

      NotHPOsFreeText: No respiratory support

    2. 10

      Case10: Male, 2.5 yr onset, 3 yr diagnosis, 13 yr report

      CasePresentingHPOs: HP:0001371 (Contractures)

      HPOsFreeText: FVC z-score sitting -3.01 (66% pred), FVC z-score supine -4.09 (54% pred), 84% MRC Scale, 1960 CK U/l, 8.6 GAA activity (nmol/h/mg)^h from cultured fibroblasts

      NotHPOsFreeText: No wheelchair used, No respiratory support

    1. 6

      Case6: Male, 36 years onset, 45 years diagnosis, 68 years report, France

      CasePresentingHPOs: HP:0002540, HP:0002878, HP:0004887, HP:0002093 (Inability to walk, Respiratory failure, Respiratory failure requiring assisted ventilation, Respiratory insufficiency)

      HPOsFreeText: Lost ambulation at 54 years, Started invasive ventilation at 52 years, Started ERT given every other week at a dose of 20 mg/kg at 63 years for 56 months, Peak Anti-rhGAA antibodies at 1:51,200, FVC at 0.7/18 (L / % expected), MIP at 9 (cm H2O), MEP at 13 (cm H2O), Time off ventilation stayed constant at 240 min, Total Motor Function Measure from 49 to 35, 6MWT from 50 to 10 meters

      CaseNotHPOs: HP:0030148 (Heart murmur)

      NotHPOsFreeText: No adverse reaction to ERT was recorded

      CaseAddInfo: Late Onset Pompe Disease, Patient died before publication

    2. 8

      Case8: Female, 36 years onset, 43 years diagnosis, 60 years report, France

      CasePresentingHPOs: HP:0002540, HP:0002878, HP:0004887 (Inability to walk, Respiratory failure, Respiratory failure requiring assisted ventilation)

      HPOsFreeText: Lost ambulation at 51 years, Started invasive ventilation at 53 years, Started ERT given every other week at a dose of 20 mg/kg at 55 years for 63 months, Peak Anti-rhGAA antibodies at 1:12,800, Time off ventilation stayed constant at 0 min, Total Motor Function Measure from 45 to 40, 6MWT stayed constant at 0 meters

      CaseNotHPOs: HP:0030148 (Heart murmur)

      NotHPOsFreeText: No adverse reaction to ERT was recorded

      CaseAddInfo: Late Onset Pompe Disease

    1. 14

      Patient14: 48yo

      CasePresentingHPOs: HP:0003325, HP:0002093, HP:0004944

      HPOsFreeText: GAA = 6.5%, BMI = 20.3, MCA M1 tract aneurysm (2mm), normal CT

      CaseNotHPOs:

      NotHPOsFreeText: No cardiovascular risk

      CaseAddInfo: 28yr disease duration, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NC_000017.11:g.(?80118193)(80118357_?)del

      ClinVar: 456368, https://www.ncbi.nlm.nih.gov/clinvar/variation/456368/

      gnomAD: n/a

    2. 12

      Patient12: 53yo

      CasePresentingHPOs: HP:0003325, HP:0002093, HP:0002315

      HPOsFreeText: morning headache, GAA = 5%, BMI = 27.4, left ventricular artery dominant, subcortical white matter lacunes

      CaseNotHPOs:

      NotHPOsFreeText: No cardiovascular risk

      CaseAddInfo: 11yr disease duration, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.670C>T (p.Arg224Trp)

      ClinVar: 189188, https://www.ncbi.nlm.nih.gov/clinvar/variation/189188/

      gnomAD: 2.53e-05, http://exac.broadinstitute.org/variant/17-78079671-C-T

    3. 13

      Case13: 56yo

      CasePresentingHPOs: HP:0003325, HP:0002093, HP:0004887, HP:0020038

      HPOsFreeText: GAA = 6.3%, BMI = 22.5, nucleo-capsular and subcortical white matter lacunes

      CaseNotHPOs:

      NotHPOsFreeText: No cardiovascular risk

      CaseAddInfo: 24yr disease duration, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.784G>A (p.Glu262Lys)

      ClinVar: 188806, https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

      gnomAD: 1.66e-05, http://exac.broadinstitute.org/variant/17-78081447-G-A

    1. P2

      PatientF3P2: Female, 36 years diagnosis, European and Native American

      CasePresentingHPOs: HP:0003236, HP:0012378, HP:0003547, HP:0009113, HP:0002910 (Increased serum CK, Fatigue, Shoulder weakness, Weak diaphragm, Increased transaminases)

      HPOsFreeText: Decline in energy and strength reported with each of her four pregnancies most prominent after her youngest daughter's diagnosis of IOPD, Subsequent enzyme assay indicated deficient GAA activity via a dried blood spot (2.2 pmol/punch/hr, control >3.88 pmol/punch/hr), Pulmonary functioning tests (PFTs) showed a decrease in forced vital capacity (FVC) from 93% predicted seated to 72% predicted supine, Laboratory results demonstrated an elevated CK level of 490 U/L (control 30–220 U/L) and mild elevation of transaminases with AST of 83 U/L (control 15–41 U/L) and ALT of 60 U/L (control 14–54 U/L)

      CaseAddInfo: Mother of proband F3P1, found to have minimally symptomatic LOPD

    1. 6/b

      Case#: 6/b, age 40, age 36 (report)

      DiseaseAssertion: gray zone (Pompe Disease)

      FamilyInfo: Family 6, no further information

      CasePresenting HPOs: HP:0001288 (Impaired gait)

      CaseHPOFreeText: Progressive worsening muscle weakness, vacuolar myopathy biopsy PAS +

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: single gene sequencing/analysis, the results of (NaG/AaGIA > 40 and %INH < 87) or (NaG/AaGIA < 40 and %INH > 87) are considered to be within a gray zone.

      Variants:

      Variant 1: NM_000152.5(GAA):c.1941C>G (p.Cys647Trp)

      ClinVar: 550327

      Variant 2:NM_000152.5(GAA):c.-32-13T>G

      ClinVar: 4027

      ParentalGenotypes: N/A

      PreviouslyPublished: N/A

    1. Here, we investigated anti-rhGAA antibody formation in a cohort of 73 adult Pompe patients during a period of 3 years of ERT. We measured their neutralizing effect on GAA enzymatic activity and cellular uptake and their impact on clinical outcome.

      GroupPresentingHPOs: HP:0005952, HP:0030197

      HPOsFreeText: LOPD confirmed by enzyme analysis in leukocytes or fibroblasts and mutation analysis, median GAA activity in leukocytes = 1.0 nmol glucose/mg hour, median GAA activity in fibroblasts = 12.9 nmol 4MU/mg hour, median MRC sum score = 80.8, 7 patients had total wheelchair dependence, 17 patients had partial wheelchair dependence, median upright FVC = 71.9%, median supine FVC = 54.0%, 4 patients required invasive ventilation, 18 required NIV, 13 patients experienced infusion associated reactions

      GroupNotHPOs:

      NotHPOsFreeText: no ERT treatments prior to study, no pregnant patients

      NumberMales: 37

      NumberFemales: 36

      CountryOrigin: n/a

      Ethnicity: n/a

      Race: n/a

      AgeRange: at symtom onset = 1.4-62.6yrs, at diagnosis = 1.4-72.7yrs, at ERT start = 26.2-74.0yrs

      TotalNumber: 73

      FamilyInfo: n/a

      NoFamily: n/a

      GroupAddInfo: all patients received ERT of 20mg/kg/2wk alglucosidase alfa intravenoulsy, minimum 5 months of treatment. Median duration of disease = 8.2yrs

      GroupPreviousTesting: anti-rhGAA antibody titers determined in plasma or serum using ELISA, neutralizing effects of antibodies determined by addition of alglucosidase alfa and patient serum to medium of GAA-deficient fibroblasts then by measurement of GAA activity in cells and medium, manual muscle testing to assess skeletal muscle strength, FVC in upright and supine positions, 46 patients developed anti-rhGAA titers about background of 1:250 (16 high, 29 intermediate, 28 low to no)

      GroupGenotypingMethod: mutation analysis (PMID: 18425781)

      Variant1: NM_000152.4(GAA):c.-32-13T>G this was carried by all but 1 patient

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      The following are the four most common variants on the second allele

      Variant2: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

      ClinVar: 4033, https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

      gnomAD: 7.041e-05, http://exac.broadinstitute.org/variant/17-78078909-CT-C

      Variant3: NC_000017.11:g.(?80118193)(80118357_?)del

      ClinVar: 456368, https://www.ncbi.nlm.nih.gov/clinvar/variation/456368/

      gnomAD: n/a

      Variant4: NM_000152.4(GAA):c.1548G>A (p.Trp516Ter)

      ClinVar: 189025, https://www.ncbi.nlm.nih.gov/clinvar/variation/189025/

      gnomAD: n/a

      Variant5: NM_000152.4(GAA):c.925G>A (p.Gly309Arg)

      ClinVar: 188797, https://www.ncbi.nlm.nih.gov/clinvar/variation/188797/

      gnomAD: 4.609e-05, http://exac.broadinstitute.org/variant/17-78081665-G-A

    1. 5

      Case5: Female, 43 years report, Italy

      CasePresentingHPOs: HP:0002355, HP:0003551, HP:0002098 (Difficulty walking, Difficulty climbing stairs, Respiratory distress)

      HPOsFreeText: Height is 1.68 m, Weight is 80 kg, BMI is 28.3 kg/cm2, 7 years on ERT, Forced Vital Capacity at 64%, Nocturnal non-invasive ventilation

      CaseAddInfo: Late Onset Pompe Disease

    1. For GAA (Pompe disease) screening

      CaseP2-GAA: female, ethnicity = North African, country origin = Morocco

      CasePresentingHPOs: HP:0010899, HP:0010916, HP:0003236

      HPOsFreeText: enzyme activity = 1.41, CPK = 682 U/L, ALT = 68 U/L, AST = 130 U/L, CRIM positive

      CaseNotHPOs:

      CaseAddInfo: heterozygote, variants in trans. Patient underwent ERT.

      CasePreviousTesting: initial and confirmatory DBS, biochemical tests, echocardiography

      CaseGenotypingMethod: mutation analyses

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: n/a

      Variant2: NM_000152.4(GAA):c.236_246delCCACACAGTGC (p.Pro79Argfs)

      ClinVar: 371302, https://www.ncbi.nlm.nih.gov/clinvar/variation/371302/

      gnomAD: n/a

    2. For GAA (Pompe disease) screening

      CaseP1-GAA: Male, ethnicity = North African, country origin = Morocco

      CasePresentingHPOs: HP:0010899, HP:0010916, HP:0003236

      HPOsFreeText: enzyme activity = 0.61, CPK = 448 U/L, ALT = 48 U/L, AST = 98 U/L, CRIM positive

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: heterozygote, variants in trans. Patient underwent ERT.

      CasePreviousTesting: initial and confirmatory DBS, biochemical tests, echocardiography

      CaseGenotypingMethod: mutation analyses

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: n/a

      Variant2: NM_000152.4(GAA):c.236_246delCCACACAGTGC (p.Pro79Argfs)

      ClinVar: 371302, https://www.ncbi.nlm.nih.gov/clinvar/variation/371302/

      gnomAD: n/a

  2. Oct 2026
    1. 1

      Case1: Male, 0.5 yr onset, 2.5 yr diagnosis, 10.04 yr report

      CasePresentingHPOs: HP:0001371 (Contractures)

      HPOsFreeText: Wheelchair used, FVC z-score sitting -0.25 (97% pred), FVC z-score supine -1.12 (87% pred), 65% MRC Scale, 530 CK U/l, 9.1 GAA activity (nmol/h/mg)^h from cultured fibroblasts

      NotHPOsFreeText: No respiratory support

    2. 7

      Case7: Male, 1 yr onset, 2 yr diagnosis, 13.7 yr report

      CasePresentingHPOs: HP:0002650 (Scoliosis)

      HPOsFreeText: Respiratory support at night, FVC z-score sitting -4.08 (54% pred), FVC z-score supine -5.4 (39% pred), 87% MRC Scale, 548 CK U/l, 17.9 GAA activity (nmol/h/mg)^h from cultured fibroblasts

      NotHPOsFreeText: No wheelchair used

    3. 3

      Case3: Female, 0.8 yr onset, 1.1 yr diagnosis, 8.9 yr report

      CasePresentingHPOs: HP:0005165 (Shortened PR interval)

      HPOsFreeText: FVC z-score sitting 0.21 (102% pred), FVC z-score supine 0.1 (101% pred), 358 CK U/l, 13.3 GAA activity (nmol/h/mg)^h from cultured fibroblasts, ECG showed delta wave suggestive of Wolff-Parkinson-White syndrome

      NotHPOsFreeText: No wheelchair used, no respiratory support

    1. Patient 5

      Case5: Female, Caucasian, United States, 2 months onset and diagnosis, 0.4 years report

      CasePresentingHPOs: HP:0011968, HP:0011469, HP:0012378, HP:0004347, HP:0010453 (Feeding difficulties, Nasal regurgitation, Fatigue, Weakness of muscles of respiration, Pelvic bone asymmetry)

      HPOsFreeText: Difficulty in lying supine while eating, sleeping and self-limited gasping episodes was observed, PT evaluation showed mild consistent asymmetry with increased lateral head tilt to the right, Tendency towards flexion/abduction/external rotation positioning of lower extremities was noted, Slight lateral thigh grooves reflected early IT band tightness with decreased posterior weight shift and propping on forearms in prone, AIMS score was at 10th percentile for chronological age and 25th to 50th percentile for corrected age, ALT 27 U/L (Normal 5–40 U/L), AST 36 U/L (Normal 15–41 U/L), ALP 352 U/L (Normal 24–170 U/L), Urinary Glc4 4.1 mmol/mol creatinine (Normal ≤8.3 mmol/mol creatinine)

      CaseNotHPOs: HP:0002033, HP:0002015, HP:0004323, HP:0003808 (Poor suck, Poor swallowing, Abnormality of body weight, Abnormal muscle tone)

      NotHPOsFreeText: CK levels, ECG, and ECHO have consistently been within normal limits, Had normal passive ranges of motion and appropriate weight bearing through lower extremities in supported standing

    2. Patient 4

      Case4: Female, Caucasian, United States, 1 month onset, 6 months diagnosis, 1.1 years report

      CasePresentingHPOs: HP:0003236, HP:0012378, HP:0006589, HP:0003725 (Increased serum CK, Fatigue, Flaring of lower rib cage, Firm muscles)

      HPOsFreeText: HyperCKemia present in the first month (505 IU/L; Normal 30–279 IU/L) but normalized spontaneously at 4 months (188 IU/L), PT assessment revealed subtle motor signs including preferred position of ring sitting with hips in flexion/abduction/external rotation and bilateral IT band tightness, Imbalanced trunk flexion, Decreased use of abdominals and excessive use of spinal extension, Asymmetry was noted in reaching objects in prone and weight shifting with lateral flexion and shortening on the left at the neck and trunk, AIMS score was at the 25th percentile and GMFM was 22.14%, Urinary Glc4 4.8 mmol/mol creatinine (Normal ≤8.3 mmol/mol creatinine)

      CaseNotHPOs: HP:0003690 (Limb muscle weakness)

      NotHPOsFreeText: She had no head lag when pulled to sit and the ability to transfer objects and bring them to midline

    3. Patient 1

      Case1: Male, Caucasian, United States, Birth onset

      CasePresentingHPOs: HP:0008872, HP:0002100, HP:0001508, HP:0008947, HP:0001655, HP:0003236, HP:0200136, HP:0001290, HP:0002835, HP:0002194 (Feeding difficulties in infancy, Recurrent aspiration pneumonia, Poor weight gain, Infantile muscular hypotonia, Patent foramen ovale, Increased serum CK, Oropharyngeal dysphagia, Low muscle tone, Aspiration, Delayed gross motor development)

      HPOsFreeText: HyperCKemia was present since the early neonatal period (378 IU/L, day 8 of life; N: 60–305 IU/L), ERT at a dose of 20 mg/kg every 2 weeks was initiated at age 1 month, CK levels were normalized on ERT by age 4 months (80 IU/L), Flexion/abduction/ external rotation positioning of lower extremities, iliotibial (IT) band tightness, lack of independent sitting, AIMS score between 10th and 25th percentile, GMFM at 23.16%, At age 23 months, he had achieved significant motor milestones; started sitting with support at 10 months and without support at 12 months, pulled to stand at 12 months, walked at 15 months and could feed himself with an immature pincer grasp. Swallow study was normal, ALT 26 U/L (Normal 5–40 U/L), AST 45 U/L (Normal 15–41 U/L), ALP 211 U/L (Normal 24–170 U/L), Urinary Glc4 3.7 mmol/mol creatinine (Normal ≤8.3 mmol/mol creatinine)

      CaseNotHPOs: HP:0011675, HP:0002910 (ECG abnormality, Elevated hepatic transaminases)

      NotHPOsFreetext:

      CaseAddInfo: Older brother of Patient 2, Late-Onset Pompe Disease

    4. Patient 2

      Case2: Male, Caucasian, United States, Birth onset

      CasePresentingHPOs: HP:0001290, HP:0200136, HP:0002033, HP:0003236, HP:0001655, HP:0002058, HP:0002194, HP:0002421, HP:0000467, HP:0002015 (Generalized hypotonia, Oral-pharyngeal dysphagia, Poor suck, Increased serum CK, Patent foramen ovale, Myopathic face, Delayed gross motor development, Poor head control, Neck muscle weakness, Dysphagia)

      HPOsFreeText: hyperCKemia at 435 IU/L on day of life 4, Patent foramen ovale detected at birth by ECHO but resolved spontaneously, PT evaluation at age 2 months revealed flexion/abduction/external rotation positioning of lower extremities with tightness bilaterally in hip flexors, hamstrings, and IT bands, Had a tendency to remain on toes when held in supported standing with additional support required for weight bearing through lower extremities, Had difficulty lifting his head in prone, with asymmetric head lift to 45 degrees, and an inability to maintain head in midline when supine, AIMS score at age 2 months was between 10–25th percentile, ALT 41 U/L (Normal 5–40 U/L), AST 33 U/L (Normal 15–41 U/L), ALP 239 U/L (Normal 24–170 U/L), Urinary Glc4 4.5 mmol/mol creatinine (Normal ≤8.3 mmol/mol creatinine)

      CaseNotHPOs: HP:0011016 (Abnormality of urine glucose concentration)

      NotHPOsFreeText:

      CaseAddInfo: Younger brother of Patient 1, Late-Onset Pompe Disease

    5. Patient 7

      Case7: Female, Caucasian, United States, 6 months diagnosis, 8 months report

      CasePresentingHPOs: HP:0001643, HP:0006699, HP:0006682, HP:0003722, HP:0008969 (Patent ductus arteriosus, Premature atrial contractions, Premature ventricular contractions, Neck flexor weakness, Leg muscle stiffness)

      HPOsFreeText: At 6 months head lag during pull to sit was noted, Had predominant overall flexion position of lower extremities with a tendency towards hip flexion/abduction/external rotation, with lateral thigh grooves suggestive of bilateral IT band tightness, AIMS score was between 10th and 25th percentile for chronological age and 50th percentile for her corrected age adjusted for prematurity while GMFM score was 16.55%, ALT 37 U/L (Normal 5–40 U/L), AST 53 U/L (Normal 15–41 U/L), ALP 174 U/L (Normal 24–170 U/L)

      CaseNotHPOs: HP:0003236, HP:0001712, HP:0001290 (Increased serum CK, Left ventricular hypertrophy, Decreased muscle tone)

      NotHPOsFreeText: Other evaluations including pulmonary, speech, and swallow were normal

    6. Patient 6

      Case6: Male, Caucasian, United States, 1 month onset, 6 months diagnosis, 8 months report

      CasePresentingHPOs: HP:0003236, HP:0001655, HP:0003701, HP:0006589, HP:0003093, (Increased serum CK, Patent foramen ovale, Proximal muscle weakness, Flaring of lower rib cage, Limited hip extension,

      HPOsFreeText: HyperCKemia was noticed in the first month (438 U/L; Normal 60–305) but normalized spontaneously by age 6 months, flexion/abduction/external rotation positioning of lower extremities and with bilateral IT band tightness was revealed at the same time, also had decreased active use of abdominal oblique muscles with a lack of active trunk rotation, Decreased active use of lower abdominal muscles with inability to achieve a posterior pelvic tilt in supine, AIMS score was at 1st percentile for age and GMFM was at 12.3%, ALT 30 U/L (Normal 5–40 U/L), AST 90 U/L (Normal 15–41 U/L), ALP 249 U/L (Normal 24–170 U/L), Urinary Glc4 2.6 mmol/mol creatinine (Normal ≤8.3 mmol/mol creatinine)

      CaseNotHPOs: HP:0001712, HP:0001290 (Left ventricular hypertrophy, Decreased muscle tone)

      NotHPOsFreeText: Other evaluations including cardiac, pulmonary, speech, and swallow were normal

    1. one confirmed LOPD patient

      Case1: Female, 55 years report, 25 years onset, Brazil, African

      CasePresentingHPOs: HP:0003325, HP:0003236, HP:0003148, HP:0100284, HP:0011807, HP:0003326, HP:0008994, HP:0002527, HP:0003551, HP:0002015, HP:0000822, HP:0000819, HP:0003119, HP:0003707, HP:0003391, HP:0003327, HP:0001315, HP:0002515, HP:0010546 (Limb-girlde muscle weakness, Increased serum CK, Elevated serum acid phosphatase, EMG: myotonic discharges, Type 1 muscle fiber atrophy, Myalgia, Proximal muscle weakness in lower limbs, Falls, Difficulty climbing stairs, Dysphagia, Hypertension, Diabetes mellitus, Dyslipidemia, Calf muscle pseudohypertrophy, Gowers sign, Axial muscle weakness, Reduced deep tendon reflexes, Waddling gait, Muscle fibrillation)

      HPOsFreeText: Serum CK 1467 U/L (normal: ≤ 200U/L), NaG/AaGIA ratio 40.4, %INH 87.2, GAA activity 4.2% from dried blood spot, Falls occurring mainly when walking for long distances, Normal Mini-Mental State Examination score (27/30), Mild symmetrical weakness in proximal muscles in the lower limbs (Medical Research Council grade 4), Needle electromyography revealed motor unit potentials with low amplitude and short duration in the iliopsoas muscle associated with fibrillation and short myotonic discharge potentials in lumbar paraspinal muscles

      CaseNotHPOs: HP:0001270 (Motor delay)

      NotHPOsFreeText: Muscle biopsy with the absence of vacuolar myopathy

      CaseAddInfo: Late-Onset Pompe Disease, One sister diagnosed with LOPD based on low GAA activity and shared genetic variants but no other known relatives with the condition

    1. 3

      Case3: Male, 19 years report, Italy

      CasePresentingHPOs: HP:0003551 (Difficulty climbing stairs)

      HPOsFreeText: Height is 1.78 m, Weight is 60 kg, BMI is 18.9 kg/cm2, 7 years on ERT, Forced Vital Capacity at 107%

      CaseNotHPOs: HP:0002098 (Respiratory distress)

      NotHPOsFreeText: Nocturnal non-invasive ventilation

      CaseAddInfo: Late Onset Pompe Disease

    2. 1

      Case1: Female, 46 years report, Italy

      CasePresentingHPOs: HP:0003551 (Difficulty climbing stairs)

      HPOsFreeText: Height is 1.64 m, Weight is 50 kg, BMI is 18.6 kg/cm2, 2 years on ERT, Forced Vital Capacity at 108%

      CaseNotHPOs: HP:0002098 (Respiratory distress)

      NotHPOsFreeText: Nocturnal non-invasive ventilation

      CaseAddInfo: Late Onset Pompe Disease

    1. II

      CaseII: Adult onset, 71 years diagnosis

      CasePresentingHPOs: HP:0003701, HP:0003326, HP:0003236, HP:0003198 (Proximal muscle weakness, Myalgia, Increased serum CK, Myopathy)

      HPOsFreeText: Plasma CK 5–10× Normal, GAA activity from dried blood spot: 0%, 6-Minute Walking Test: 40 min, Forced Vital Capacity Seated: 850 (22%)

      CaseNotHPOs: HP:0002795 (Abnormal respiration)

      CaseAddInfo: Late-Onset Pompe Disease

    2. 1

      CaseV,1: Adolescent onset, 42 years diagnosis

      CasePresentingHPOs: HP:0003701, HP:0003236, HP:0003388, HP:0003326 (Proximal muscle weakness, Increased serum CK, Easy fatigability, Myalgia)

      HPOsFreeText: Plasma CK 5-10× Normal, Vacuoles in histology, 6-Minute Walking Test: 135 min, Forced Vital Capacity Seated: 950 (20%), GAA activity from dried blood spot: 0.20%

      CaseNotHPOs: HP:0002795 (Abnormal respiration)

      CaseAddInfo: Late-Onset Pompe Disease

    3. 3

      CaseV,3: Child onset, 45 years diagnosis

      CasePresentingHPOs: HP:0003701, HP:0003236 (Proximal muscle weakness, Increased serum CK)

      HPOsFreeText: Plasma CK 2.5-5× Normal, GAA activity from dried blood spot: 0.08%, 6-Minute Walking Test: 566 min

      CaseNotHPOs: HP:0002795 (Abnormal respiration)

      CaseAddInfo: Late-Onset Pompe Disease

    4. III

      CaseIII: Adult onset, 63 years diagnosis

      CasePresentingHPOs: HP:0003701, HP:0003388, HP:0003236, HP:0003198, HP:0002460, HP:0002015 (Proximal muscle weakness, Easy fatigability, Increased serum CK, Myopathy, Distal muscle weakness, Dysphagia)

      HPOsFreeText: Plasma CK 2.5–5× Normal, GAA activity from muscle: 11.7%

      CaseNotHPOs: HP:0002795 (Abnormal respiration)

      CaseAddInfo: Late-Onset Pompe Disease

    5. I

      CaseI: Early adult onset, 49 years diagnosis

      CasePresentingHPOs: HP:0003701, HP:0003388, HP:0003236, HP:0003198 (Proximal muscle weakness, Easy fatigability, Increased serum CK, Myopathy)

      HPOsFreeText: Plasma CK 5–10× Normal, GAA activity from lymphocytes: 14.2%

      CaseNotHPOs: HP:0002795 (Abnormal respiration)

      CaseAddInfo: Late-Onset Pompe Disease

    6. 2

      CaseV,2: Adult onset, 33 years diagnosis

      CasePresentingHPOs: HP:0003701, HP:0003236, HP:0003388 (Proximal muscle weakness, Increased serum CK, Easy fatigability)

      HPOsFreeText: Plasma CK 5-10× Normal, 6-Minute Walking Test: 566 min, Forced Vital Capacity Seated: 3000 (90%), GAA activity from dried blood spot: 0.20%

      CaseNotHPOs: HP:0002795 (Abnormal respiration)

      CaseAddInfo: Late-Onset Pompe Disease

    1. 62-year-old man

      Case1: Male, 62 years report

      CasePresentingHPOs: HP:0002091, HP:0002878, HP:0003701, HP:0040047, HP:0002098, HP:0100786, HP:0006510, HP:0005978, HP:0000822, HP:0003124, HP:0001677, HP:0003236, HP:0004324, HP:0002329, HP:0030207, HP:0002098, HP:0040047, HP:0100750, HP:0002097, HP:0007269, HP:0040046 (Restrictive lung disease, Respiratory failure, Proximal muscle weakness, Abnormality of the right hemidiaphragm, Shortness of breath, Hypersomnia, Chronic obstructive pulmonary disease, Diabetes mellitus Type II, Hypertension, Hypercholesterolemia, Coronary artery disease, Elevated serum creatine kinase, Increased body weight, Drowsiness, Paradoxical respiration, Respiratory distress, Abnormality of the right hemidiaphragm, Atelectasis, Emphysema, Spinal muscular atrophy, Abnormality of the left hemidiaphragm)

      HPOsFreeText: Hypercapnic respiratory failure, Chronic phrenic neuropathy bilaterally, Long history of apparently idiopathic right hemidiaphragm paralysis, Underwent muscle biopsy and electromyography, both of which showed nonspecific myopathic features associated with mild denervation, On presentation, the patient's vital signs were a temperature of 36.5 °C (97.7 °F); heart rate, 94 beats/minute; blood pressure, 104/70 mm Hg; respiratory rate, 22 breaths/minute; oxygen saturation, 90% when receiving 2 L of supplemental oxygen per minute; and body mass index, 29.9 kg/m2, Decreased air entry bilaterally, Laboratory values were: Hemoglobin, 120 g/L; platelets, 279 × 109/L; white blood cells, 7.7 × 109/L; sodium, 140 mmol/L; potassium, 5.1 mmol/L; bicarbonate, 40 mmol/L; serum urea nitrogen, 3.6 mmol/L; creatinine, 70.7 μmol/L; and calcium, 2.48 mmol/L, Fatty atrophy of rotator cuff musculature, Tests for resting room-air arterial blood gases showed a pH of 7.29; PCO2, 89.4 mm Hg; PO2, 67.6 mm Hg; and serum bicarbonate, 43 mmol/L, Right diaphragm paralysis, Electromyography showed complete absence of phrenic compound muscle action potentials bilaterally. No activation of motor unit potentials was seen within the diaphragm, either with respiration or with volitional effort. Ultrasonography showed that the left hemidiaphragm was hyperechoic, 0.14 cm thick at functional residual capacity (FRC), with a thickening ratio of 1.1 (the thickening ratio is thickness at total lung capacity/thickness at FRC). The right hemidiaphragm was hyperechoic, 0.15 cm thick at FRC, with thickening ratio of 0.9. (Normal thickness is >0.15 cm, normal thickening ratio is >1.2.) The aldolase concentration was slightly increased at 9 U/L (reference level, <7.7 U/L). To complete the evaluation for rarer causes of diaphragmatic dysfunction, neurology services requested testing for inherited neuropathies. Three weeks later, the patient's serum GAA level was 1.0 nmol/mL/hour (reference level, >7.4 nmol/mL/hour)

      CaseNotHPOs: HP:0003549 (Abnormality of connective tissue)

      NotHPOsFreeText: The following tests were within reference range: creatine kinase, thyroid function tests, erythrocyte sedimentation rate, serum and protein electrophoresis, antinuclear antibody profile, and anti-Jo antibodies

      CaseAddInfo: Ex-Smoker with 40–80 pack-years of smoking, Medications at presentation to facility included aspirin, clopidogrel, simvastatin, diltiazem, sitagliptin, metformin, budesonide and formoterol inhaler, tiotropium bromide inhaler, and albuterol inhaler

    1. 1117

      Case1117: Male, 35 years onset, Welsh/English, Caucasian

      CasePresentingHPOs: HP:0003560, HP:0005110 (Muscular dystrophy, Atrial fibrillation)

      HPOsFreeText: 1,000 –2000's CK level, Immunohistochemistry: dystrophin, sarcoglycans, merosin

      CaseNotHPOs: HP:0009051, HP:0002540 (Increased muscle glycogen content, Non-ambulatory)

    1. Patient Number 3

      Case3: Male, 35 years report, 5 years onset, Algeria, African

      CasePresentingHPOs: HP:0003323, HP:0003749, HP:0002355, HP:0007340, HP:0008956, HP:0003484, HP:0003236, HP:0003198 (Progressive muscle weakness, Pelvic girdle muscle weakness, Difficulty walking, Lower limb muscle weakness, Proximal lower limb amyotrophy, Upper limb muscle weakness, Increased serum CK, Myopathy)

      HPOsFreeText: At grade 3 of Vignos and Walton scales, CK rate was 5 times the normal value and AST and ALT were normal, EMG was compatible with a myopathic disorder, GAA activity measured in leukocytes was significantly decreased

      CaseNotHPOs: HP:0003115, HP:0003116, HP:0001270, HP:0001290, HP:0002240, HP:0001640, HP:0005952, HP:0002540 (Abnormal ECG, Abnormal echocardiography, Motor delay, Generalized hypotonia, Hepatomegaly, Cardiomegaly, Decreased pulmonary function, Non-ambulatory)

    1. 12

      Case12: Male, 35 years onset, 50 years diagnosis, 61 years report, France

      CasePresentingHPOs: HP:0002540, HP:0002878, HP:0004887 (Inability to walk, Respiratory failure, Respiratory failure requiring assisted ventilation)

      HPOsFreeText: Lost ambulation at 48 years, Started invasive ventilation at 35 years, Started ERT given every other week at a dose of 20 mg/kg at 56 years for 49 months, Peak Anti-rhGAA antibodies at 1:1600, FVC at 0 (L / % expected), MIP at 22 (cm H2O), MEP at 28 (cm H2O), Time off ventilation stayed constant at 0 min, 6MWT stayed constant at 0 meters

      CaseNotHPOs: HP:0030148 (Heart murmur)

      NotHPOsFreeText: No adverse reaction to ERT was recorded

      CaseAddInfo: Late Onset Pompe Disease

    2. 3

      Case3: Male, 28 years onset, 30 years diagnosis, 69 years report, France

      CasePresentingHPOs: HP:0002540, HP:0002878, HP:0004887, HP:0002093 (Inability to walk, Respiratory failure, Respiratory failure requiring assisted ventilation, Respiratory insufficency)

      HPOsFreeText: Lost ambulation at 58 years, Started invasive ventilation at 28 years, Started ERT given every other week at a dose of 20 mg/kg at 68 years for 11 months, Peak Anti-rhGAA antibodies at 1:1600, FVC at 0.45/13 (L / % expected), MIP at 17 (cm H2O), MEP at 29 (cm H2O), Time off ventilation stayed constant at 0, Total Motor Function Measure from 31 to 27

      CaseNotHPOs: HP:0030148 (Heart murmur)

      NotHPOsFreeText: No adverse reaction to ERT was recorded

      CaseAddInfo: Late Onset Pompe Disease, Patient died before publication

    3. 4

      Case4: Female, 20 years onset, 48 years diagnosis, 57 years report, France

      CasePresentingHPOs: HP:0002540, HP:0002878, HP:0004887 (Inability to walk, Respiratory failure, Respiratory failure requiring assisted ventilation)

      HPOsFreeText: Lost ambulation at 42 years, Started invasive ventilation at 32 years, Started ERT given every other week at a dose of 20 mg/kg at 50 years for 87 months, Peak Anti-rhGAA antibodies at 1:25,600, FVC at 0.42/13 (L / % expected), MIP at 15 (cm H2O), MEP at 17 (cm H2O), Time off ventilation increased from 60 to 120 min, Total Motor Function Measure from 45 to 49, 6MWT from 10 to 30 meters

      CaseNotHPOs: HP:0030148 (Heart murmur)

      NotHPOsFreeText: No adverse reaction to ERT was recorded

      CaseAddInfo: Late Onset Pompe Disease

    1. The affected patient

      Case1: Male, French-Canadian, 18 years onset, 54 years diagnosis and report

      CasePresentingHPOs: HP:0008994, HP:0000822, HP:0003119, HP:0004398, HP:0007185, HP:0009109, HP:0002094, HP:0012764, HP:0002098 (Proximal muscle weakness in lower limbs, High blood pressure, dyslipidemia, Peptic ulcer, Loss of consciousness, Denervation of the diaphragm, Dyspnea, Orthopnea, Shortness of breath)

      HPOsFreeText: Dependent on continuous positive airway pressure or bilevel positive airway pressure when he is lying flat or sleeping because of previous intubation and tracheostomy, GAA activity measured from dried blood spot was 0.87 pmol/h/punch (Normal 4.96 - 27.3)

      CaseAddInfo: Late Onset Pompe Disease, The patient’s mother had six miscarriages and died at age 75 of lung cancer and his father died of cardiac problems in his early sixties, It appears that no other family members, including his parents and two siblings, were affected, patient had a previous appendectomy, He has no allergies, stopped smoking in 2002, and denied any alcohol or drug use

    1. 9

      Case9: Male, 46 years onset, 48 years diagnosis, Italy

      HPOsFreeText: See Group Phenotypes, ERT started at 48, GAA Activity at ~7.5 pmol/min/mg before ERT and ~11 after

      GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.525delT (p.Glu176Argfs*45)

      ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

      gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 http://gnomad.broadinstitute.org/variant/17-78078909-CT-C


      CaseAddInfo: Late Onset Pompe Disease

    2. 8

      Case8: Male, 16 years onset, 36 years diagnosis, Italy

      HPOsFreeText: See Group Phenotypes, ERT started at 36, GAA Activity at ~5 pmol/min/mg before ERT and ~13 after

      GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.525delT (p.Glu176Argfs*45)

      ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

      gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 http://gnomad.broadinstitute.org/variant/17-78078909-CT-C


      CaseAddInfo: Late Onset Pompe Disease

    3. 18

      Case18: Female, 50 years onset, 53 years diagnosis, Italy

      HPOsFreeText: See Group Phenotypes, ERT started at 56, GAA Activity at ~6 pmol/min/mg before ERT and ~9 after

      GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1465G>A (p.Asp489Asn)

      ClinVar: 92465 https://www.ncbi.nlm.nih.gov/clinvar/variation/92465/

      gnomAD: European (Finnish) 4.621e-5, Overall 1.195e-5 http://gnomad.broadinstitute.org/variant/17-78084553-G-A


      CaseAddInfo: Late Onset Pompe Disease

    4. 3

      Case3: Male, 30 years onset, 66 years diagnosis, Italy

      HPOsFreeText: See Group Phenotypes, ERT started at 67, GAA Activity at ~8 pmol/min/mg before ERT and ~10 after

      GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1927G>A (p.Gly643Arg)

      ClinVar: 4023 https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

      gnomAD: European (Non-Finnish) 3.667e-5, Overall 2.479e-5 http://gnomad.broadinstitute.org/variant/17-78086713-G-A


      CaseAddInfo: Late Onset Pompe Disease

    5. 1

      Case1: Male, 21 years onset, 31 years diagnosis, Italy

      HPOsFreeText: See Group Phenotypes, ERT started at 31, GAA Activity at ~7.5 pmol/min/mg before ERT and ~8 after

      GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1927G>A (p.Gly643Arg)

      ClinVar: 4023 https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

      gnomAD: European (Non-Finnish) 3.667e-5, Overall 2.479e-5 http://gnomad.broadinstitute.org/variant/17-78086713-G-A


      CaseAddInfo: Late Onset Pompe Disease

    6. 13

      Case13: Male, 34 years onset, 45 years diagnosis, Italy

      HPOsFreeText: See Group Phenotypes, ERT started at 45, GAA Activity at ~10 pmol/min/mg before ERT and ~10.5 after

      GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.525delT (p.Glu176Argfs*45)

      ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

      gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 http://gnomad.broadinstitute.org/variant/17-78078909-CT-C


      CaseAddInfo: Late Onset Pompe Disease

    7. 2

      Case2: Female, 42 years onset, 51 years diagnosis, Italy

      HPOsFreeText: See Group Phenotypes, ERT started at 32, GAA Activity at ~10 pmol/min/mg before ERT and ~11 after

      GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1076-1G>C

      CAID: CA401364879 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1076-1G%3EC

      gnomAD: Not in gnomAD


      CaseAddInfo: Late Onset Pompe Disease

    8. 17

      Case17: Female, 30 years onset, 39 years diagnosis, Italy

      HPOsFreeText: See Group Phenotypes, ERT started at 41

      GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Paper does not specify what kind of mutation this is. Mentions only that it is a "Loss of transcript" mutation

      Variant2: NM_000152.4:c.2331+1

      ClinVar: N/A

      gnomAD: N/A


      CaseAddInfo: Late Onset Pompe Disease

    1. 7

      Patient7: 71yo

      CasePresentingHPOs: HP:0003325, HP:0002093, HP:0002315, HP:0004887, HP:0000822, HP:0003141, HP:0002870, HP:0020038

      HPOsFreeText: morning headache, GAA = 7%, BMI = 28.3, temporo-insular lacunes

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 18yr disease duration, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.3:c.2530_2541del

      CAID: CA658795292, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA658795292

      gnomAD: n/a

    2. 5

      Patient5: 36yo

      CasePresentingHPOs: HP:0003325, HP:0002093, HP:0001513, HP:0002637

      HPOsFreeText: GAA = 4.6%, BMI = 35.1, normal CTA, right temporal pole ischaemia

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 4yr disease duration, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.3:c.2530_2541del

      CAID: CA658795292, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA658795292

      gnomAD: n/a

    3. 21

      Patient21: 68yo

      CasePresentingHPOs: HP:0003325, HP:0002093, HP:0003141, HP:0001513, HP:0020038

      HPOsFreeText: GAA = 30%, BMI = 30.3, nucleo-capsular and subcortical white matter lacunes

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 30yr disease duration

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

    4. 8

      Patient8: 47yo

      CasePresentingHPOs: HP:0003325, HP:0001513

      HPOsFreeText: GAA = 5%, BMI = 30.8, Normal CTA and CT

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 2yr disease duration, variants in cis

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.1551+1G>C

      ClinVar: 554983, https://www.ncbi.nlm.nih.gov/clinvar/variation/554983/

      gnomAD: n/a

    1. #4

      Case#: Subject number 4, female, 11 years (report)

      DiseaseAssertion: Pompe disease

      FamilyInfo: No known family member with PD

      CasePresentingHPOs: HP:0001638 (cardiomyopathy), HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness)

      CaseHPOFreeText:

      CaseNotHPOs: HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

      CaseNotHPOFreeText: no biopsy, not asymptomatic

      CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

      glucosidase activity: GAA activity was 0.16 mol/Lh in dried blood spots (normal range >0.75).

      Variant 1: NM_000152.5(GAA):c.-32-13T>C

      Variant 1 ClinVarID: 4027

      Variant 1 CAid: CA116606

      Variant 2: NM_000152.5(GAA):c.1831G>A (p.Gly611Ser)

      Variant 2 ClinVarID: 935199

      Variant 2 CAid: CA401369553

      Zygosity: Compound heterozygous

      ParentalGenotype: N/A

      PreviouslyPublished: N/A

    2. #11

      Case#: Subject number 11, male, 51 years (report)

      DiseaseAssertion: Pompe disease

      FamilyInfo: No known family member with PD

      CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002153 (hyperkalemia)

      CaseHPOFreeText:

      CaseNotHPOs: HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0001638 (cardiomyopathy), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

      CaseNotHPOFreeText: no biopsy, not asymptomatic

      CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

      glucosidase activity: GAA activity was 0.21 mol/Lh in dried blood spots (normal range >0.75).

      Variant 1: NM_000152.5(GAA):c.-32-13T>C

      Variant 1 ClinVarID: 4027

      Variant 1 CAid: CA116606

      Variant 2: NM_000152.5(GAA):c.2104C>T (p.Arg702Cys)

      Variant 2 ClinVarID: 189040

      Variant 2 CAid: CA274304

      Zygosity: Compound heterozygous

      ParentalGenotype: N/A

      PreviouslyPublished: N/A

    3. #15

      Case#: Subject number 15, male, 58 years (report)

      DiseaseAssertion: Pompe disease

      FamilyInfo: No known family member with PD

      CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0002153 (hyperkalemia)

      CaseHPOFreeText:

      CaseNotHPOs: HP:0001252 (Hypotonia), HP:0002094 (dyspnoea), HP:0001638 (cardiomyopathy), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress)

      CaseNotHPOFreeText: no biopsy, not asymptomatic

      CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

      glucosidase activity: GAA activity was 0.31 mol/Lh in dried blood spots (normal range >0.75).

      Variant 1: NM_000152.5(GAA):c.-32-13T>C

      Variant 1 ClinVarID: 4027

      Variant 1 CAid: CA116606

      Variant 2: NM_000152.5(GAA):c.655G>A (p.Gly219Arg)

      Variant 2 ClinVarID: 189065

      Variant 2 CAid: CA274334

      Zygosity: Compound heterozygous

      ParentalGenotype: N/A

      PreviouslyPublished: N/A

    1. 6

      Case#: Subject number 6(L)

      DiseaseAssertion: Late Onset Pompe disease

      FamilyInfo: N/A

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: CK testing: 176 U/L (28-300 U/L is normal), AST: 61 U/L (24-72 U/L is normal), ALT: 39 U/L (17-63 U/L is normal), Hex4: 5.9 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

      glucosidase activity: GAA activity #1 was 1.32 micromole/L/h and GAA activity #2 (NBS) 0.88 in dried blood spots (>2.10 micromole/L/h is normal). 0.7 in confirmatory testing (>6.7 is normal).

      Variant 1: NM_000152.5(GAA):c.-32-13T>G

      Variant 1 ClinVarID: 4027

      Variant 1 CAid: CA116606

      Variant 2: NM_000152.5(GAA):c.-32-13T>G

      Variant 2 ClinVarID: 4027

      Variant 2 CAid: CA116606

      Zygosity: homozygous

      ParentalGenotype: N/A

      PreviouslyPublished: N/A

    1. c.743T > C(p.Leu248Pro)

      Case84

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.743T>C (p.Leu248Pro)

      CAID: CA401363263 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.743T%3EC

      gnomAD: European (Non-Finnish) 1.551e-5, Overall 7.079e-6 http://gnomad.broadinstitute.org/variant/17-78081406-T-C


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Adult Late Onset Pompe Disease

    2. c.953T > C(p.Met318Thr)

      Case55

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.953T>C (p.Met318Thr)

      ClinVar: 4021 https://www.ncbi.nlm.nih.gov/clinvar/variation/4021/

      gnomAD: African 8.608e-5, Overall 4.485e-5 http://gnomad.broadinstitute.org/variant/17-78081693-T-C


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Juvenile Late Onset Pompe Disease

    3. c.2481+102_2646+31del (p.Gly828_Asn882del)

      Case72

      HPOsFreeText: See Group Phenotypes


      CasePreviousTesting: Sanger sequencing

      CaseMethod1: Sanger sequencing and PCR Amplification

      CaseMethod2: Whole Exome Sequencing (WES)

      CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.


      Variant1: NM_000152.4:c.2481+102_2646+31del (p.Gly828_Asn882del) (exon 18 del)

      ClinVar: 4031 https://www.ncbi.nlm.nih.gov/clinvar/variation/4031/

      gnomAD: Not in gnomAD


      Variant2: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      CaseAddInfo: Adult Late Onset Pompe Disease, 4 other patients have the same genotype

    1. P20

      Patient20: Male, 19yo

      CasePresentingHPOs:

      HPOsFreeText: LOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 19yr disease duration, ERT lasted 132mo

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

      ClinVar: 4033, https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

      gnomAD: 0.00009959, http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

    2. P11

      Patient11: Male, 45yo

      CasePresentingHPOs: HP:0000822, HP:0003077

      HPOsFreeText: LOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: 6yr disease duration, ERT lasted 17mo

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.3:c.832_833del

      CAID: CA913184772, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA913184772

      gnomAD: n/a

    1. 14

      Case#: Subject number 14, male, 63 years (report), 47 years (onset), 58 years (diagnosis)

      DiseaseAssertion: Pompe disease

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0000365 (hearing loss), HP:0000360 (tinnitus)

      CaseHPOFreeText: On BiPAP, ambulatory, assistive device (cane)

      CaseNotHPOs: HP:0000821, HP:0002650, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0001638 (hypothyroidism, scoliosis, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, cardiomyopathy)

      CaseNotHPOFreeText: no infusion reaction, no tracheostomy

      CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy

      Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)

      Variant 1 ClinVarID: 4027

      Variant 1 CAid: CA116606

      Variant 2: NM_000152.5(GAA):c.1445C>G

      Variant 2 ClinVarID: N/A

      Variant 2 CAid: CA401366794

      Zygosity: Compound heterozygous

      ParentalGenotype: N/A

      PreviouslyPublished: N/A

    1. Detailed characteristics of these patients

      Patient2: female, 16yo, juvenile onset

      CasePresentingHPOs:

      HPOsFreeText: LOPD, BMI = 17.7;20.3;20.3, WGMS = 2;2;2

      CaseNotHPOs: HP:0002355

      NotHPOsFreeText: did not require respiratory support

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1:NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.307T>G (p.Cys103Gly)

      ClinVar: 92483, https://www.ncbi.nlm.nih.gov/clinvar/variation/92483/

      gnomAD: n/a

    2. Detailed characteristics of these patients

      Patient10: male, 18yo, juvenile onset

      CasePresentingHPOs:

      HPOsFreeText: LOPD, BMI = 15.2 / 16.5 / n-a, WGMS = 0 / 0 /n-a

      CaseNotHPOs: HP:0002355

      NotHPOsFreeText: did not require respiratory support

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

      ClinVar: 4033, https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

      gnomAD: 0.00009959, http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

    3. Detailed characteristics of these patients

      Patient11: female, 49yo, adult onset

      CasePresentingHPOs:

      HPOsFreeText: LOPD, BMI = 21 / 19.4 / 20.2, WGMS = 2 / 2-3 / 3

      CaseNotHPOs: HP:0002355

      NotHPOsFreeText: did not require respiratory support

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.3:c.1291_1299del

      CAID: CA658795248, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA658795248

      gnomAD: n/a

    1. 2

      Case# Patient 2, male

      CasePresentingHPOs: HP:0003236, HP:0003325

      CaseAddInfo: 66 at onset, 72 at diagnosis

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

      ClinVar: 4033

      gnomAD: 7.041e-05, http://exac.broadinstitute.org/variant/17-78078909-CT-C

    2. Clinical and laboratory features of the 17 newly diagnosed patients with LOPD

      GroupPresentingHPOs: HP:0003325, HP:0003457, HP:0012548, HP:0004887, HP:0010535, HP:0001712, HP:0031296

      HPOsFreeText: hyperCKaemia+LGMW, BMI, mean (SD) 25.2±5.8, Serum CK, mean (SD) 600±302, vacuolar myopathy, Muscle GAA %, mean (SD) 9.4±3.8, myogenic EMG, abnormal MRI, %Predicted FVC, mean (SD) 73±11, 6MWT, mean (SD) 452±9, vacuolisation of myofibers with variable glycogen storage, AP staining low in 6 individuals, medium in five, and high in 2 individuals. Low residual GAA activity in muscles,

      GroupNotHPOs:

      NotHPOsFreeText:

      NumberMales: 8

      NumberFemales: 9

      CountryOrigin: n/a

      AgeRange: mean (SD) 40±14.36

      TotalNumber: 14

      GroupAddInfo: mean age at disease onset was 40±14.3 years, median age at disease diagnosis was 47±14 years. 14 of the individuals underwent enzyme replacement therapy. Blood CK levels increased in all but one individual.

      GroupGenotypingMethod: GAA gene sequencing

      Variant 1: NM_000152.4(GAA):c.-32-13T>G

      ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant 2: p.P522A, NM_000152.4(GAA):c.1564C>G (p.Pro522Ala)

      ClinVar: 371277, https://www.ncbi.nlm.nih.gov/clinvar/variation/371277/

      gnomAD: n/a

    3. 4

      Case# Patient 4, female

      CasePresentingHPOs: HP:0003236, HP:0003325

      CaseAddInfo: 31yo at onset, 40yo at diagnosis

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NM_000152.4(GAA):c.1564C>G (p.Pro522Ala)

      ClinVar: 371277, https://www.ncbi.nlm.nih.gov/clinvar/variation/371277/

      gnomAD: n/a

    1. 10

      Family 10 - Patient 10

      FamilyPresentingHPOs: HP:0007340, HP:0003701, HP:0003327, HP:0040081, HP:0002111

      HPOsFreeText: muscle pathology with vacuolar myopathy

      FamilyNotHPOs: HP:0010628, HP:0002015, HP:0003691, HP:0003306, HP:0002650

      Ethnicity: Iranian

      ProbandLabel:

      FamilyAddInfo: onset at 38yo, diagnosis at 50yo, MRC sum score = 73, patient required use of NIV

      FamilyPreviousTesting: Respiratory Evaluation: FVC = 65%, CK = 551 U/L, muscle pathology examined, DBS enzyme activity (with inhibition) = 0.12 μmol/L/h

      FamilyGenotypingMethod: GAA analyzed with Sanger Sequencing for entire coding region and conserved exon-intron splice junctions, PCR performed for deletion screening

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NM_000152.3:c.2596delG

      CAID: CA891834514, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA891834514

      gnomAD: n/a

    2. 4a

      Family 4 - Patients 4a and 4b

      FamilyPresentingHPOs: HP:0007340, HP:0003701, HP:0000467, HP:0003327, HP:0010628, HP:0002015, HP:0003306, HP:0002111, HP:0011807, HP:0003554, HP:0002111, HP:0100298, HP:0040081

      HPOsFreeText: myopathic muscle unit action potentials, 4b muscular pathology with mild atrophy of type 1 and 2 fibers with many moth‐eaten fibers, no vacuoles, no glycogen excess

      FamilyNotHPOs: HP:0003691, HP:0002650

      NotHPOsFreeText:

      Ethnicity: Iranian

      ProbandLabel: 4a, female, 7yo at onset, 30yo at diagnosis

      FamilyAddInfo: 4b (male) dx at 23yo, 4a MRC sum score = 84, 4b MRC sum score = 86, both patients required use of NIV

      FamilyPreviousTesting: Respiratory Evaluation: 4a FVC = 29%, 4b FVC = 66%, 4a CK = 760 U/L, 4b CK = 3,257 U/L, muscle pathology (examined only in 4b), DBS enzyme activity (with inhibition) for 4a = 0.1 μmol/L/h, for 4b = 0.13 μmol/L/h, NCS, EMG

      FamilyGenotypingMethod: GAA analyzed with Sanger Sequencing for entire coding region and conserved exon-intron splice junctions, PCR performed for deletion screening

      VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      VariantAllele2: NM_000152.3:c.1650delG

      Clinvar: n/a

      CAID: CA627699787, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA627699787

      gnomAD: n/a

    1. For GAA (Pompe disease) screening,

      CaseP5-GAA: female, ethnicity = South Asian, country origin = Nepal

      CasePresentingHPOs:

      HPOsFreeText: enzyme activity = 2.27

      CaseNotHPOs: HP:0010899, HP:0010916, HP:0003236

      CaseAddInfo: known pseudodeficiency allele (c.1726G>A)

      CasePreviousTesting: initial and confirmatory DBS, biochemical tests

      CaseGenotypingMethod: mutation analyses

      Variant: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: n/a

    1. Case22: Female, 46 years report

      HPOsFreeText: 3 years of ERT completed, 6 Minute Walking Test at 73 meters, Forced Vital Capacity at 68%

      GenotypingMethod: GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1819_1836del (p.Gly607_His612del )

      CAID: CA658795266 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1819_1836del

      gnomAD: Not in gnomAD


      CaseAddInfo: Late Onset Pompe Disease

    2. Case11: Male, 57 years report

      HPOsFreeText: 9 years of ERT completed, 6 Minute Walking Test at 210 meters, Forced Vital Capacity at 31%

      GenotypingMethod: GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.525delT (p.Glu176Argfs*42)

      ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

      gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 http://gnomad.broadinstitute.org/variant/17-78078909-CT-C


      CaseAddInfo: Late Onset Pompe Disease

    3. Case18: Male, 66 years report

      HPOsFreeText: 9 years of ERT completed, 6 Minute Walking Test at 290 meters, Forced Vital Capacity at 45%

      GenotypingMethod: GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1047del (p.Ser349Argfs)

      CAID: CA891862612 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1047del

      gnomAD: Not in gnomAD


      CaseAddInfo: Late Onset Pompe Disease

    4. Case25: Male, 67 years report

      HPOsFreeText: 4 years of ERT completed, 6 Minute Walking Test at 172 meters, Forced Vital Capacity at 49%

      GenotypingMethod: GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.-32-3C>G

      CAID: CA658795220 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.-32-3C%3EG

      gnomAD: Not in gnomAD


      CaseAddInfo: Late Onset Pompe Disease

    5. Case21: Female, 49 years report

      HPOsFreeText: 8 years of ERT completed, Forced Vital Capacity at 59%

      GenotypingMethod: GAA Gene Sequencing


      Variant1: NM_000152.4:c.-32-13T>G

      ClinVar: 4027 http://www.ncbi.nlm.nih.gov/clinvar/variation/4027

      gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G


      Variant2: NM_000152.4:c.1819_1836del (p.Gly607_His612del )

      CAID: CA658795266 http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1819_1836del

      gnomAD: Not in gnomAD


      CaseAddInfo: Late Onset Pompe Disease

    1. to assess the potential effects of AMO treatment on GAA normal spliced mRNA expression and activity, as well as on the pathological phenotype in muscle cells, we obtained myoblasts from a LO-GSDII patient who presented the c.-32-13T > G mutation in compound heterozygosity with the c.2646_2646+1delTG mutation in exon 18

      Patient2: myoblasts from this patient were used to measure the effects of AMO tratment on GAA normal spliced mRNA expression/activity and the pathological phenotype in muscle cells. Under basal conditions, these myotubes retained 20% of enzymatic activity compared to WT. AMO treatment partially restored the correctly splice variant of GAA mRNA (confirmed via real-time PCR).

      CasePresentingHPOs:

      HPOsFreeText: LOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: n/a

      CaseGenotypingMethod: comparative DNA vs. mRNA sequencing

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.3:c.2646_2647del

      CAID: CA913184745, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA913184745

      gnomAD: n/a

    1. 13

      Patient13: Male, 46yo at diagnosis, 47yo at ERT

      CasePresentingHPOs:

      HPOsFreeText: anti rh-GAA antibodies titre = 1:25,699, enzyme (μmol/g/h) = 0.52 (3-20)

      CaseNotHPOs:

      NotHPOsFreeText: NIV and mobility aid not required

      CaseAddInfo: 6yr disease duration, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.3:c.482_483del

      CAID: CA8814879, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA8814879

      gnomAD: 1.729e-05, http://exac.broadinstitute.org/variant/17-78078864-TCC-T

    2. 16

      Patient16: Female, 37yo at diagnosis and ERT

      CasePresentingHPOs:

      HPOsFreeText: anti rh-GAA antibodies titre = neg, enzyme (μmol/g/h) = 0.18 (3-20), mobility aid required before and after ERT

      CaseNotHPOs:

      NotHPOsFreeText: NIV not required

      CaseAddInfo: 21yr disease duration

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

    3. 5

      Patient5: Female, 38yo at diagnosis, 40yo at ERT

      CasePresentingHPOs:

      HPOsFreeText: anti rh-GAA antibodies titre = neg, enzyme (μmol/g/h) = 0.8 (3-20)

      CaseNotHPOs:

      NotHPOsFreeText: NIV and mobility aid not used

      CaseAddInfo: 26yr disease duration, variants in trans

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

      Variant2: NM_000152.3:c.482_483del

      CAID: CA8814879, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA8814879

      gnomAD: 1.729e-05, http://exac.broadinstitute.org/variant/17-78078864-TCC-T

    1. 5

      Patient5: male, Romanian

      CasePresentingHPOs: HP:0003677, HP:0003236, HP:0003325, HP:0003418, HP:0008997

      HPOsFreeText: CK > 10x increase, CK = 1500 U/L, reduced alpha-glucosidase activity

      CaseNotHPOs: HP:0002093

      CaseAddInfo: onset in middle age, enzyme activity also reduced in daughter

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.2066_2070dupAGCCG (p.Ala691Serfs)

      ClinVar: 92471, https://www.ncbi.nlm.nih.gov/clinvar/variation/92471/

      gnomAD: n/a

      Variant2: NM_000152.4(GAA):c.-32-13T>G

      Clinvar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

      gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

    1. LOPD patient #1

      Case#: LOPD patient #1, Male, 69, ethnicity unknown.

      DiseaseAssertion: Pompe disease

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0002094, HP:0006554, HP:0012378, HP:0001324 (Dyspnea, Acute respiratory failure, Fatigue, Lower Girdle Muscle Weakness and Upper Girdle Muscle Weakness)

      CaseHPOFreeText: Dyspnea was present during exercise, not at rest. Lower Girdle Muscle Weakness and Upper Girdle Muscle Weakness share the same HPO.

      CaseNotHPOs:

      CaseNotHPOFreeText: Patient has normal creatine phosphokinase levels, No Dyspnea at rest, No Ortopnea, No Airways infections, no myalgia

      CasePreviousTesting: GAA gene sequencing to asses genotype.

      GAA activity was reduced (0.36 microMol/L/h) in reference to standard (10.1 ± 6.6 microMol/L/h) This was measured by dried blood spot .

      GAA muscle activity was 3.6 pmol/min/mg, no reference range was provided

      Variant: Variant 1: NM_000152.5:c.-32-13T>G

      ClinVar: 4027

      CAID: CA116606

      gnomAD: MAF= 0.005541 (Ashkenazi Jewish)

      Variant 2: NM_000152.5(GAA):c.1564C>G (p.Pro522Ala)

      ClinVar:371277

      CAID:CA16041893

      gnomAD: N/A

      ParentalGenotype: N/A

      PreviouslyPublished: N/A