4,371 Matching Annotations
  1. Last 7 days
    1. c.1099T > C(p.Trp367Arg)

      Case28

      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.1099T>C (p.Trp367Arg)

      ClinVar: 555820 https://www.ncbi.nlm.nih.gov/clinvar/variation/555820/

      gnomAD: Not in gnomAD


      Variant2: NM_000152.4:c.1802C>T (p.Ser601Leu)

      ClinVar: 194154 https://www.ncbi.nlm.nih.gov/clinvar/variation/194154/

      gnomAD: East Asian 6.418e-4, Overall 3.187e-5 http://gnomad.broadinstitute.org/variant/17-78086424-C-T


      CaseAddInfo: Infantile Onset Pompe Disease

    2. c.655G > A(p.Gly219Arg)

      Case47

      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.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


      Variant2: NM_000152.4:c.1979G>A (p.Arg660His)

      ClinVar: 189172 https://www.ncbi.nlm.nih.gov/clinvar/variation/189172/

      gnomAD: African 2.546e-4, Overall 3.680e-5 http://gnomad.broadinstitute.org/variant/17-78086765-G-A


      CaseAddInfo: Infantile Onset Pompe Disease

    3. 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

    4. c.2512C > T(p.Gln838*)

      Case42

      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.2512C>T (p.Gln838*)

      ClinVar: 92479 https://www.ncbi.nlm.nih.gov/clinvar/variation/92479/

      gnomAD: African 6.177e-5, Overall 3.997e-6 http://gnomad.broadinstitute.org/variant/17-78092022-C-T


      Variant2: NM_000152.4:c.2105G>T (p.Arg702Leu)

      CAID: 92472 https://www.ncbi.nlm.nih.gov/clinvar/variation/92472/

      gnomAD: Not in gnomAD


      CaseAddInfo: Infantile Onset Pompe Disease

    5. c.1942G > A(p.Gly648Ser)

      Case34

      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.


      Variant: NM_000152.4:c.1942G>A (p.Gly648Ser)

      ClinVar: 188902 https://www.ncbi.nlm.nih.gov/clinvar/variation/188902/

      gnomAD: South Asian 3.365e-4, Overall 5.361e-5 http://gnomad.broadinstitute.org/variant/17-78086728-G-A


      CaseAddInfo: Infantile Onset Pompe Disease, Patient is homozygous for this variant

    6. 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

    7. 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

    8. c.1978C > T(p.Arg660Cys)

      Case10

      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.1978C>T (p.Arg660Cys)

      ClinVar: 558604 https://www.ncbi.nlm.nih.gov/clinvar/variation/558604/

      gnomAD: East Asian 5.554e-5, Overall 4.142e-6 http://gnomad.broadinstitute.org/variant/17-78086764-C-T


      Variant2: NM_000152.4:c.2221G>A (p.Asp741Asn)

      ClinVar: 571521 https://www.ncbi.nlm.nih.gov/clinvar/variation/571521/

      gnomAD: East Asian 1.087e-4, Overall 7.971e-6 http://gnomad.broadinstitute.org/variant/17-78090798-G-A


      CaseAddInfo: Infantile Onset Pompe Disease

    9. c.1411_1414del4(p.Glu471fs*5)

      Case27

      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.1411_1414delGAGA (p.Glu471fs*5)

      ClinVar: 188874 https://www.ncbi.nlm.nih.gov/clinvar/variation/188874/

      gnomAD: East Asian 2.513e-4, Overall 1.781e-5 http://gnomad.broadinstitute.org/variant/17-78083827-CGAGA-C


      Significance of this variant is unknown.

      Variant2: NM_000152.4:c.460_465del (Arg154_Thre155del)

      ClinVar: 551306 https://www.ncbi.nlm.nih.gov/clinvar/variation/551306/

      gnomAD: Not in gnomAD


      CaseAddInfo: Infantile Onset Pompe Disease

    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

    11. c.1933G > A(p.Asp645Asn)

      Case32

      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.


      Variant: NM_000152.4:c.1933G>A (p.Asp645Asn)

      ClinVar: 188728 https://www.ncbi.nlm.nih.gov/clinvar/variation/188728/

      gnomAD: African 6.599e-5, Overall 8.250e-6 http://gnomad.broadinstitute.org/variant/17-78086719-G-A


      CaseAddInfo: Infantile Onset Pompe Disease, Patient is homozygous for this variant, 1 more patient has the same genotype

    12. c.2560C > T(p.Arg854*)

      Case21

      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.2560C>T (p.Arg854*)

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

      gnomAD: African 1.891e-3, Overall 2.090e-4 http://gnomad.broadinstitute.org/variant/17-78092070-C-T


      Variant2: NM_000152.4:c.1129G>C (p.Gly377Arg)

      ClinVar: 497033 https://www.ncbi.nlm.nih.gov/clinvar/variation/497033/

      gnomAD: European (Non-Finnish) 2.356e-5, Overall 1.072e-5 http://gnomad.broadinstitute.org/variant/17-78082341-G-C


      CaseAddInfo: Infantile Onset Pompe Disease

    1. 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

    2. 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

    3. 6

      Patient6: Male, 36yo at diagnosis, 40yo at ERT

      CasePresentingHPOs:

      HPOsFreeText: anti rh-GAA antibodies titre = neg, enzyme (μmol/g/h) = 1.2 (2-10)

      CaseNotHPOs:

      NotHPOsFreeText: NIV and mobility aid not used

      CaseAddInfo: 11yr disease duration

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: NM_000152.4(GAA):c.1437G>A (p.Lys479=)

      ClinVar: 188044, https://www.ncbi.nlm.nih.gov/clinvar/variation/188044/

      gnomAD: n/a

    4. 15

      Patient15: Female, 48yo at diagnosis and ERT

      CasePresentingHPOs:

      HPOsFreeText: anti rh-GAA antibodies titre = 1:1600, enzyme (μmol/g/h) = 0.48 (3-20), NIV required only after ERT

      CaseNotHPOs:

      NotHPOsFreeText: mobility aid not required

      CaseAddInfo: 33yr disease duration

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: NM_000152.4(GAA):c.1437G>A (p.Lys479=)

      ClinVar: 188044, https://www.ncbi.nlm.nih.gov/clinvar/variation/188044/

      gnomAD: n/a

    5. 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

    6. 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

    7. 4

      Patient 4: Male, 37yo at diagnosis, 41yo at ERT

      CasePresentingHPOs:

      HPOsFreeText: anti rh-GAA antibodies titre = neg, enzyme (μmol/g/h) = 2.1 (3-20), mobility aid required before and after ERT

      CaseNotHPOs:

      NotHPOsFreeText: NIV not used

      CaseAddInfo: 10yr disease duration

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: NM_000152.4(GAA):c.1437G>A (p.Lys479=)

      ClinVar: 188044, https://www.ncbi.nlm.nih.gov/clinvar/variation/188044/

      gnomAD: n/a

    8. 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. PD/VOUS-1

      CasePD/VOUS-1: 3 weeks diagnosis

      HPOsFreeText: GAA activity 3.6 (nmol · h−1 · mg−1), Mean percentage of normal 5.0%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      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


      Variant3: NM_000152.4:c.664G>A (p.Val222Met)

      ClinVar: 290223 https://www.ncbi.nlm.nih.gov/clinvar/variation/290223/

      gnomAD: South Asian 5.393e-3, Overall 6.931e-4 http://gnomad.broadinstitute.org/variant/17-78079665-G-A


      CaseAddInfo: Patient has one pseudodeficency allele and one allele of uncertain significance, Nomenclature claims Variant 1 and 2 are in cis

    2. PD/Pathogenic-8

      CasePD/Pathogenic-8: 2 weeks diagnosis

      HPOsFreeText: GAA activity 5.0 (nmol · h−1 · mg−1), Mean percentage of normal 7.0%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      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


      Variant3: NM_000152.4:c.692+5G>T

      ClinVar: 526532 https://www.ncbi.nlm.nih.gov/clinvar/variation/526532/

      gnomAD: European (Non-Finnish) 9.003e-6, Overall 4.181e-6 http://gnomad.broadinstitute.org/variant/17-78079698-G-T


      CaseAddInfo: Patient has one pseudodeficency allele and one pathogenic allele, Nomenclature claims Variant 1 and 2 are in cis

    3. LOPD-8

      CaseLOPD-8: 6 weeks diagnosis

      HPOsFreeText: GAA activity 2.9 (nmol · h−1 · mg−1), Mean percentage of normal 4.1%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.2051C>T (p.Pro684Leu)

      ClinVar: 285821 https://www.ncbi.nlm.nih.gov/clinvar/variation/285821/

      gnomAD: European (Non-Finnish) 1.631e-4, Overall 8.195e-5 http://gnomad.broadinstitute.org/variant/17-78087027-C-T


      Variant2: NM_000152.3: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

    4. 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

    5. PD/Pathogenic-2

      CasePD/Pathogenic-2: 3 weeks diagnosis

      HPOsFreeText: GAA activity 8.8 (nmol · h−1 · mg−1), Mean percentage of normal 12.4%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      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


      Variant3: NM_000152.4:c.2646+2T>A

      ClinVar: 188924 https://www.ncbi.nlm.nih.gov/clinvar/variation/188924/

      gnomAD: Not in gnomAD


      CaseAddInfo: Patient has one pseudodeficency allele and one pathogenic allele, Nomenclature claims Variant 1 and 2 are in cis

    6. 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

    7. PD/VOUS-3

      CasePD/VOUS-3: 2 weeks diagnosis

      HPOsFreeText: GAA activity 11.3 (nmol · h−1 · mg−1), Mean percentage of normal 15.8%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      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


      Variant3: NM_000152.4:c.664G>A (p.Val222Met)

      ClinVar: 290223 https://www.ncbi.nlm.nih.gov/clinvar/variation/290223/

      gnomAD: South Asian 5.393e-3, Overall 6.931e-4 http://gnomad.broadinstitute.org/variant/17-78079665-G-A


      CaseAddInfo: Patient has one pseudodeficency allele and one allele of uncertain significance, Nomenclature claims Variant 1 and 2 are in cis

    8. 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

    9. PD/VOUS-2

      CasePD/VOUS-2: 2 weeks diagnosis

      HPOsFreeText: GAA activity 16.6 (nmol · h−1 · mg−1), Mean percentage of normal 23.3%

      GenotypingMethod: Newborn Screening Panels


      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      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


      Variant3: NM_000152.4:c.2069C>T (p.Pro690Leu)

      ClinVar: 424308 https://www.ncbi.nlm.nih.gov/clinvar/variation/424308/

      gnomAD: East Asian 1.077e-4, Overall 2.337e-5 http://gnomad.broadinstitute.org/variant/17-78087045-C-T


      CaseAddInfo: Patient has one pseudodeficency allele and one allele of uncertain significance, Nomenclature claims Variant 1 and 2 are in cis

    10. 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. 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

    2. 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

    3. 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

    4. 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

    5. 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

    6. 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

    7. 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. 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/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

    2. 5/a

      Case#: 5/a, age 6, age 1 (report)

      DiseaseAssertion: Pompe Disease

      FamilyInfo: Family 5, no further information

      CasePresenting HPOs: HP:0001290, HP:0001639 (hypotonia, hypertrophic cardiomyopathy)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: single gene sequencing/analysis, 94.50 NaG/AaGIA, 94.31% inhibition of GAA; NaG/AaGIA above 40 and %INH above 87 are in the affected range

      Variants:

      Variant 1:NM_000152.5(GAA):c.1832G>A (p.Gly611Asp)

      ClinVar: 371226

      Variant 2:NM_000152.5(GAA):c.1832G>A (p.Gly611Asp)

      ClinVar: 371226

      ParentalGenotypes: N/A

      PreviouslyPublished: N/A

    3. 3

      Case#: 3, age 48, age 41 (report)

      DiseaseAssertion: Pompe Disease

      FamilyInfo: Family 3, no further information

      CasePresenting HPOs:HP:0012378, HP:0003546, HP:0001324 (fatigue, exercise intolerance, muscle weakness)

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: single gene sequencing/analysis, 63.85 NaG/AaGIA, 91% inhibition of GAA; NaG/AaGIA above 40 and %INH above 87 are in the affected range

      Variants:

      Variant 1:NM_000152.5(GAA):c.-32-3C>A

      ClinVar: 371622

      Variant 2:NM_000152.5(GAA):c.-32-3C>A

      ClinVar: 371622

      ParentalGenotypes: N/A

      PreviouslyPublished: N/A

    4. 4

      Case#: 4, age 24, age 18 (report)

      DiseaseAssertion: Pompe Disease

      FamilyInfo: Family 4, no further information

      CasePresenting HPOs:HP:0012378, HP:0003546, HP:0001324 (fatigue, exercise intolerance, muscle weakness)

      CaseHPOFreeText: vacuolar myopathy biopsy PAS +

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: single gene sequencing/analysis, 40.54 NaG/AaGIA, 90.54% inhibition of GAA; NaG/AaGIA above 40 and %INH above 87 are in the affected range

      Variants:

      Variant 1:NM_000152.5(GAA):c.2608C>T (p.Arg870Ter)

      ClinVar: 189009

      Variant 2: not reported

      ParentalGenotypes: N/A

      PreviouslyPublished: N/A

    5. 2/a

      Case#: 2/a, age 20, age 14 (report)

      DiseaseAssertion: Pompe Disease

      FamilyInfo: Family 2, no further information

      CasePresenting HPOs:HP:0002878, HP:0012378, HP:0003546, HP:0001324 (Respiratory failure, fatigue, exercise intolerance, muscle weakness)

      CaseHPOFreeText: valvular myopathy, biopsy with vacuolar myopathy with PAS +

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: single gene sequencing/analysis, 64.47 NaG/AaGIA, 92.28% inhibition of GAA; NaG/AaGIA above 40 and %INH above 87 are in the affected range

      Variants:

      Variant 1:NM_000152.5(GAA):c.377G>A (p.Trp126Ter)

      ClinVar: 932904

      Variant 2: NM_000152.5(GAA):c.1655T>C (p.Leu552Pro)

      ClinVar: 279811

      ParentalGenotypes: N/A

      PreviouslyPublished: N/A

    1. 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. 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

    2. 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. 38

      Patient38: Male, 20 years report, 2 year onset

      CasePresentingHPOs: HP:0001324, HP:0002098, HP:0002527 (Muscle weakness, Respiratory distress, Falls)

      HPOsFreeText: GAA activity 2.7% from leukocyte, Wheelchair needed, Respiratory Assistance needed

      CaseNotHPOs: HP:0001640, HP:0002240 (Cardiomegaly, Hepatomegaly)

      NotHPOsFreeText: N/A

      CaseAddInfo: LOPD

    2. 22

      Patient22: Male, 30 years report, 23 year onset

      CasePresentingHPOs: HP:0001324, HP:0002098 (Muscle weakness, Respiratory distress)

      HPOsFreeText: GAA activity 1.1% from leukocyte, Wheelchair needed

      CaseNotHPOs: HP:0001640, HP:0002240 (Cardiomegaly, Hepatomegaly)

      NotHPOsFreeText: Respiratory Assistance not needed

      CaseAddInfo: LOPD

    3. 16

      Patient16: Female, 36 years report, 28 years onset

      CasePresentingHPOs: HP:0001324 (Muscle weakness)

      HPOsFreeText: GAA activity 1% from a dried blood spot

      CaseNotHPOs: HP:0002098, HP:0002240, HP:0001640 (Respiratory distress, Hepatomegaly, Cardiomegaly)

      NotHPOsFreeText: No wheelchair needed, Respiratory Assistance not needed

      CaseAddInfo: LOPD

    1. In the present study, we describe the clinical course and provide a molecular analysis of another 25 mainland Chinese patients with IOPD, and we identified c.2662G > T (p.Glu888X) as the most common mutation in northern Chinese patients. These data collectively lay a foundation for understanding the clinical and genetic features of mainland Chinese patients with IOPD.

      GroupPresentingHPOs: HP:0001324, HP:0001270, HP:0002205, HP:0002098, HP:0001635, HP:0001640, HP:0011968

      HPOsFreeText: IOPD, reduced GAA activity, paucity of movements

      GroupNotHPOs:

      NumberMales: 14

      NumberFemales: 11

      CountryOrigin: mainland China; 12 patients from southern China, 13 from northern China

      Ethnicity: Chinese

      Race: Chinese

      AgeRange: median age at symptom onset = 3.4mo, median age at diagnosis = 4.9mo

      *TotalNumber: 25

      FamilyInfo: Parents of those individuals with mutations were sequenced

      NoFamily: n/a

      GroupAddInfo: all patients diagnosed with IOPD between 2013 and 2016 at Shanghai Children's Medical Center. Of the 24 untreated patients, non survived beyond 1.5yrs, only surviving (Patient 25) was 7mo at last follow-up.

      GroupPreviousTesting: IOPD diagnosed via reduced GAA enzyme activity in leukocytes or DBS (PMID: 16702880)

      GroupGenotypingMethod: DNA isolated from blood samples, coding exons (2-20) and intron/exon boundaries of GAA gene amplified via PCR (primers: PMID: 10338092), resulting DNA was sequenced with ABI3730XL sequencer then was analyzed with Mutation Survey or DNA Variant Analysis software, novel mutations were screened in 60 normal individuals (120 alleles) via direct sequencing and no novel variants were found among these suggesting those found in study patients are uncommon polymorphisms.

      fragments containing a mutation in the patients were amplified and sequenced for the corresponding parents

      Phylogenetic conservation of missense mutations analyzed with ClustalX program, and pathogenicity of novel variants predicited with MutationTaster, sorting intolerant from tolerant (SIFT), and PolyPhen-2

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

      this was identified (by present study) as the most common variant in northern Chinese patients, heterozygous for 5 patients, homozygous for one patient

      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. PD23

      Patient23: Male, Southern China

      CasePresentingHPOs:

      HPOsFreeText: IOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.1411_1414delGAGA (p.Glu471Profs)

      ClinVar: 188874, https://www.ncbi.nlm.nih.gov/clinvar/variation/188874/

      gnomAD: 1.688e-05, http://exac.broadinstitute.org/variant/17-78083827-CGAGA-C

      Variant2: NM_000152.4(GAA):c.2024_2026delACA (p.Asn675del)

      ClinVar: 189006, https://www.ncbi.nlm.nih.gov/clinvar/variation/189006/

      gnomAD: 2.105e-05, http://exac.broadinstitute.org/variant/17-78086806-CACA-C

    3. PD08

      Patient8: Male, Southern China

      CasePresentingHPOs:

      HPOsFreeText: IOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.1411_1414delGAGA (p.Glu471Profs)

      ClinVar: 188874, https://www.ncbi.nlm.nih.gov/clinvar/variation/188874/

      gnomAD: 1.688e-05, http://exac.broadinstitute.org/variant/17-78083827-CGAGA-C

    4. PD05

      Patient5: Male, northern China

      CasePresentingHPOs:

      HPOsFreeText: IOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: homozygous

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: 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

    5. PD01

      Patient1: Female, northern China

      CasePresentingHPOs:

      HPOsFreeText: IOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: 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

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

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

      gnomAD: 0.00002479, http://gnomad.broadinstitute.org/variant/17-78086713-G-A

    6. PD07

      Patient7: Female, Southern China

      CasePresentingHPOs:

      HPOsFreeText: IOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.1432G>A (p.Gly478Arg)

      ClinVar: 551295, https://www.ncbi.nlm.nih.gov/clinvar/variation/551295/

      gnomAD: 8.525e-06, http://exac.broadinstitute.org/variant/17-78083849-G-A

      Variant2: NM_000152.4(GAA):c.1802C>T (p.Ser601Leu)

      ClinVar: 194154, https://www.ncbi.nlm.nih.gov/clinvar/variation/194154/

      gnomAD: n/a

    7. PD04

      Patient4: Female, southern China

      CasePresentingHPOs:

      HPOsFreeText: IOPD

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

      ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

      gnomAD: 0.0001721, http://exac.broadinstitute.org/variant/17-78086721-C-A

      Variant2: NM_000152.4(GAA):c.2185delC (p.Leu729Trpfs) **this is not the same protein transcript listed in paper (p.Thr729fsX8) but I could not find this in clinvar or allele registry)

      ClinVar: 370552, https://www.ncbi.nlm.nih.gov/clinvar/variation/370552/https://www.ncbi.nlm.nih.gov/clinvar/variation/370552/

      gnomAD: 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. 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. P4

      Patient4: Male, 2mo at diagnosis, 2.5mo at ERT

      CasePresentingHPOs:

      HPOsFreeText: classic IOPD, poor response to ERT, Pompe muscle pathology score = 4.1, Glycogen = 40.3 Vv(PAS + /mf)%, larger empty vacuoles = 52.2 Vv (LEV/mf)%, Autophagic vacuoles = 0 %/mf

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: biopsy taken from  musculus vastus lateralis

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.2213G>A (p.Trp738Ter)

      ClinVar: 370222, https://www.ncbi.nlm.nih.gov/clinvar/variation/370222/

      gnomAD: n/a

      Variant2: NM_000152.4:c.delExon18

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

      gnomAD: n/a

    1. 26/F

      Patient26: Female

      CasePresentingHPOs: HP:0004887, HP:0001270, HP:0001371

      HPOsFreeText: CRIM positive, Anti-rh GGA antibodies maximum titer = ≤ 1:400, heart normalization

      CaseNotHPOs: HP:0025156, HP:0002546, HP:0000365

      NotHPOsFreeText: infusion associated reaction

      CaseAddInfo: variants in trans, symptom onset at 3yo, diagnosis at 5yo, ERT at 8yo

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.1064T>C (p.Leu355Pro)

      ClinVar: 284093, https://www.ncbi.nlm.nih.gov/clinvar/variation/284093/

      gnomAD: 0.000007972, http://gnomad.broadinstitute.org/variant/17-78082197-T-C

    2. 14/M

      Patient14: male

      CasePresentingHPOs: HP:0004887, HP:0040288, HP:0002546, HP:0000365

      HPOsFreeText: CRIM negative, Anti-rh GGA antibodies maximum titer = 1:204.800, immunomodulation, infusion associated reaction, able to sit independently, partial heart normalization

      CaseNotHPOs: HP:0001371

      CaseAddInfo: homozygous variants in trans. Symptom onset, diagnosis and ERT at 4yo.

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

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

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

      gnomAD: n/a

    3. 17/M

      Patient17: Male

      CasePresentingHPOs: HP:0004887, HP:0011471, HP:0001270, HP:0002546

      HPOsFreeText: CRIM negative, tracheostomy, heart normalization

      CaseNotHPOs: HP:0000365, HP:0001371

      NotHPOsFreeText: infusion associated reaction

      CaseAddInfo: homozygous variants in trans, symptom onset at 2yo, diagnosis and ERT at 6yo

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: NM_000152.4(GAA):c.1A>G (p.Met1Val)

      ClinVar: 188785, https://www.ncbi.nlm.nih.gov/clinvar/variation/188785/

      gnomAD: n/a

    4. 12/M

      Patient 12: male

      CasePresentingHPOs:

      HPOsFreeText: CRIM positive, infusion associated reaction, heart normalization

      CaseNotHPOs: HP:0004887, HP:0025156, HP:0002355, HP:0002546, HP:0000365, HP:0001371

      CaseAddInfo: variants in trans, symptom onset at 2yo, diagnosis at 3yo, ERT at 4yo

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.236_246delCCACACAGTGC (p.Pro79Argfs)

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

      gnomAD: n/a

      Variant2: NM_000152.4(GAA):c.1655T>C (p.Leu552Pro)

      ClinVar: 279811, https://www.ncbi.nlm.nih.gov/clinvar/variation/279811/

      gnomAD: 1.663e-05, http://exac.broadinstitute.org/variant/17-78085800-T-C

    5. 8/F

      Patient8: Female

      CasePresentingHPOs: HP:0004887, HP:0001270

      HPOsFreeText: CRIM positive, tracheostomy partial heart normalization

      CaseNotHPOs: HP:0025156, HP:0001371

      NotHPOsFreeText: infusion associated reaction

      CaseAddInfo: variants in trans, symptom onset at 1yo, diagnosis at 9yo, ERT at 10yo. Died due to infusion reaction with ERT.

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: 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

      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

    6. 18/M

      Patient18: Male

      CasePresentingHPOs: HP:0004887, HP:0001270, HP:0002546

      HPOsFreeText: CRIM positive, Anti-rh GGA antibodies maximum titer = ≤ 1:400, heart normalization

      CaseNotHPOs: HP:0025156, HP:0000365, HP:0001371

      NotHPOsFreeText: infusion associated reaction

      CaseAddInfo: homozygous variants in trans, symptom onset at 1yo, diagnosis at 1.5yo, ERT at 4yo

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: 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

    7. 5/F

      Patient5: female

      CasePresentingHPOs: HP:0001270

      HPOsFreeText: CRIM negative, Anti-rh GGA antibodies maximum titer = 1:25.600, infusion associated reaction, heat normalization

      CaseNotHPOs: HP:0004887, HP:0025156, HP:0001371

      CaseAddInfo: homozygous variants in trans, symptom onset and diagnosis at 1yo, ERT at 2yo. Died due to infusion reaction with ERT.

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

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

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

      gnomAD: n/a

    8. 13/F

      Patient13: female

      CasePresentingHPOs: HP:0004887, HP:0011471, HP:0001270, HP:0002546, HP:0000365

      HPOsFreeText: CRIM positive, tracheostomy, partial heart normalization

      CaseNotHPOs: HP:0001371

      NotHPOsFreeText: infusion associated reaction

      CaseAddInfo: variants in trans, symptom onset at 6yo, diagnosis and ERT at 11yo

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.236_246delCCACACAGTGC (p.Pro79Argfs)

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

      gnomAD: n/a

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

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

      gnomAD: 5.884e-05, http://exac.broadinstitute.org/variant/17-78086713-G-A

    1. 44

      Case44: Male, 10yo at onset, 15yo at enrollment

      CasePresentingHPOs: HP:0007340, HP:0003701, HP:0003327, HP:0003236, HP:0002111, HP:0100748, HP:0003458

      HPOsFreeText: symmetric muscle weakness of extremities, CK = 3313 IU/L, FVC = 23%, Unspecific myopathic change, DBS GAA activity = 0.1, mixed leukocyte GAA activity = 1.80

      CaseNotHPOs: HP:0001627, HP:0002086

      NotHPOsFreeText:

      CaseAddInfo: 5 years between onset and diagnosis

      CasePreviousTesting: clinical history, laboratory data, DBS and ML assays to measure GAA activity, electromyography, muscle pathology analysis

      CaseGenotypingMethod: full sequencing of GAA gene

      VariantAllele1: NM_000152.4(GAA):c.546G>T (p.Thr182=)

      ClinVar: 370637, https://www.ncbi.nlm.nih.gov/clinvar/variation/370637/

      gnomAD: n/a

      VariantAllele2: NM_000152.4(GAA):c.1316T>A (p.Met439Lys)

      ClinVar: 371305, https://www.ncbi.nlm.nih.gov/clinvar/variation/371305/

      gnomAD: 3.988e-05, http://exac.broadinstitute.org/variant/17-78082617-T-A

    1. 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:

    2. 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:

    3. 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:

    4. 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:

    5. 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. 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

    1. 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

    2. 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

    3. 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. CaseLP2-9: Male, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 0.44 umol/hr/L, Serum CK at 140 U/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification


      Variant1: NM_000152.4:c.752C>T (p.Ser251Leu)

      ClinVar: 325781 https://www.ncbi.nlm.nih.gov/clinvar/variation/325781/

      gnomAD: East Asian 2.760e-3, Overall 3.540e-4 http://gnomad.broadinstitute.org/variant/17-78081415-C-T


      Variant2: NM_000152.4:c.761C>T (p.Ser254Leu)

      ClinVar: 325782 https://www.ncbi.nlm.nih.gov/clinvar/variation/325782/

      gnomAD: East Asian 2.759e-3, Overall 1.947e-4 http://gnomad.broadinstitute.org/variant/17-78081424-C-T


      Variant3: NM_000152.4:c.1411_1414delGAGA (p.Glu471Profs)

      ClinVar: 188874 https://www.ncbi.nlm.nih.gov/clinvar/variation/188874/

      gnomAD: East Asian 2.513e-4, Overall 1.781e-5 http://gnomad.broadinstitute.org/variant/17-78083827-CGAGA-C


      Variant4: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      CaseAddInfo: Late Onset Pompe Disease, Nomenclature indicates Variants 1 and 2 and Variants 3 and 4 are in cis

    2. CaseLP-3: Female, Taiwan, Birth diagnosis

      HPOsFreeText: 4MU enzyme activity at 0.49, MS/MS ennzyme activity at 0.10

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification


      Variant1: NM_000152.4:c.752C>T (p.Ser251Leu)

      ClinVar: 325781 https://www.ncbi.nlm.nih.gov/clinvar/variation/325781/

      gnomAD: East Asian 2.760e-3, Overall 3.540e-4 http://gnomad.broadinstitute.org/variant/17-78081415-C-T


      Variant2: NM_000152.4:c.761C>T (p.Ser254Leu)

      ClinVar: 325782 https://www.ncbi.nlm.nih.gov/clinvar/variation/325782/

      gnomAD: East Asian 2.759e-3, Overall 1.947e-4 http://gnomad.broadinstitute.org/variant/17-78081424-C-T


      Variant3: NM_000152.4:c.1004G>A (p.Gly335Glu)

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

      gnomAD: Not in gnomAD


      CaseAddInfo: Suspected Late Onset Pompe Disease, Nomenclature indicates Variants 1 and 2 are in cis

    3. CaseLP2-6: Female, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 0.10 umol/hr/L, Serum CK at 103 U/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification


      Variant1: NM_000152.4:c.752C>T (p.Ser251Leu)

      ClinVar: 325781 https://www.ncbi.nlm.nih.gov/clinvar/variation/325781/

      gnomAD: East Asian 2.760e-3, Overall 3.540e-4 http://gnomad.broadinstitute.org/variant/17-78081415-C-T


      Variant2: NM_000152.4:c.761C>T (p.Ser254Leu)

      ClinVar: 325782 https://www.ncbi.nlm.nih.gov/clinvar/variation/325782/

      gnomAD: East Asian 2.759e-3, Overall 1.947e-4 http://gnomad.broadinstitute.org/variant/17-78081424-C-T


      Variant3: NM_000152.4:c.1004G>A (p.Gly335Glu)

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

      gnomAD: Not in gnomAD


      CaseAddInfo: Late Onset Pompe Disease, Nomenclature indicates Variants 1 and 2 are in cis

    4. CaseOPOPD-64: Male, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 0.72 umol/hr/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification

      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

      Variant2: NM_000152.4:c.2024_2026delACA (p.Asn675del)

      ClinVar: 189006 https://www.ncbi.nlm.nih.gov/clinvar/variation/189006/

      gnomAD: East Asian 1.106e-4, Overall 8.275e-6 http://gnomad.broadinstitute.org/variant/17-78086806-CACA-C

      CaseAddInfo: One Pompe Mutation allele and One Pseudodeficency Mutation allele, 3 other people have this genotype

    5. CaseOPOPD-43: Female, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 1.20 umol/hr/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification


      Variant1: NM_000152.4:c.1082C>T (p.Pro361Leu)

      ClinVar: 403712 https://www.ncbi.nlm.nih.gov/clinvar/variation/403712/

      gnomAD: Latino 5.798e-5, Overall 1.203e-5 http://gnomad.broadinstitute.org/variant/17-78082294-C-T


      Variant2: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      CaseAddInfo: One Pompe Mutation allele and One Pseudodeficency Mutation allele

    6. CaseOPTPD-78: Male, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 0.91 umol/hr/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification


      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      Variant2: NM_000152.4:c.2214G>A (p.Trp738Ter)

      ClinVar: 370223 https://www.ncbi.nlm.nih.gov/clinvar/variation/370223/

      gnomAD: East Asian 5.437e-5, Overall 3.986e-6 http://gnomad.broadinstitute.org/variant/17-78090791-G-A


      CaseAddInfo: One Pompe Mutation allele and Two Pseudodeficency Mutation alleles, Nomenclature indicates patient is homozygous for Variant 1 and Variant 2 is in cis with one copy

    7. CaseOPOPD-61: Female, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 0.63 umol/hr/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification


      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      Variant2: NM_000152.4:c.2024_2026delACA (p.Asn675del)

      ClinVar: 189006 https://www.ncbi.nlm.nih.gov/clinvar/variation/189006/

      gnomAD: East Asian 1.106e-4, Overall 8.275e-6 http://gnomad.broadinstitute.org/variant/17-78086806-CACA-C


      CaseAddInfo: One Pompe Mutation allele and One Pseudodeficency Mutation allele, 3 other people have this genotype

    8. CaseOPOPD-63: Male, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 1.05 umol/hr/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification

      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

      Variant2: NM_000152.4:c.2024_2026delACA (p.Asn675del)

      ClinVar: 189006 https://www.ncbi.nlm.nih.gov/clinvar/variation/189006/

      gnomAD: East Asian 1.106e-4, Overall 8.275e-6 http://gnomad.broadinstitute.org/variant/17-78086806-CACA-C

      CaseAddInfo: One Pompe Mutation allele and One Pseudodeficency Mutation allele, 3 other people have this genotype

    9. CaseOPOPD-72: Male, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 1.31 umol/hr/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification


      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      Variant2: NM_000152.4:c.2662G>T (p.Glu888Ter)

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

      gnomAD: East Asian 2.719e-4, Overall 1.998e-5 http://gnomad.broadinstitute.org/variant/17-78092467-G-T


      CaseAddInfo: One Pompe Mutation allele and One Pseudodeficency Mutation allele, 2 other patients have the same genotype

    10. CaseOPOPD-38: Female, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 0.56 umol/hr/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification


      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.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      CaseAddInfo: One Pompe Mutation allele and One Pseudodeficency Mutation allele

    11. CaseOPTPD-1: Female, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 1.47 umol/hr/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification


      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      Variant2: NM_000152.4:c.546+5G>T

      ClinVar: 557811 https://www.ncbi.nlm.nih.gov/clinvar/variation/557811/

      gnomAD: East Asian 4.978e-4, Overall 3.824e-5 http://gnomad.broadinstitute.org/variant/17-78078936-G-T


      CaseAddInfo: One Pompe Mutation allele and Two Pseudodeficency Mutation alleles, Nomenclature indicates patient is homozygous for Variant 1 and Variant 2 is in cis with only one copy, 2 other patients have the same genotype

    12. CaseIP2-4: Female, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 0.08 umol/hr/L, Serum CK at 385 U/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification


      Variant1: NM_000152.4:c.1194+2T>C

      ClinVar: 370077 https://www.ncbi.nlm.nih.gov/clinvar/variation/370077/

      gnomAD: Not in gnomAD


      Variant2: NM_000152.4:c.1935C>A (p.Asp645Glu)

      ClinVar: 4029 https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

      gnomAD: East Asian 1.729e-3, Overall 1.240e-4 http://gnomad.broadinstitute.org/variant/17-78086721-C-A


      Variant3: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A


      CaseAddInfo: Infantile Onset Pompe Disease, Nomenclature indicates Variant 1 and 2 are in trans, also that Variant 3 is in cis with only one of them

    13. CaseLP2-10: Male, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 0.06 umol/hr/L, Serum CK at 670 U/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification


      Variant1: NM_000152.4:c.752C>T (p.Ser251Leu)

      ClinVar: 325781 https://www.ncbi.nlm.nih.gov/clinvar/variation/325781/

      gnomAD: East Asian 2.760e-3, Overall 3.540e-4 http://gnomad.broadinstitute.org/variant/17-78081415-C-T


      Variant2: NM_000152.4:c.761C>T (p.Ser254Leu)

      ClinVar: 325782 https://www.ncbi.nlm.nih.gov/clinvar/variation/325782/

      gnomAD: East Asian 2.759e-3, Overall 1.947e-4 http://gnomad.broadinstitute.org/variant/17-78081424-C-T


      Variant3: NM_000152.4:c.2662G>T (p.Glu888Ter)

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

      gnomAD: East Asian 2.719e-4, Overall 1.998e-5 http://gnomad.broadinstitute.org/variant/17-78092467-G-T


      CaseAddInfo: Late Onset Pompe Disease, Nomenclature indicates Variants 1 and 2 are in cis

    14. CaseOPOPD-62: Female, Taiwan, Birth diagnosis

      HPOsFreeText: GAA (MS/MS) enzyme activity at 0.85 umol/hr/L

      GenotypingMethod: GAA Gene Sequencing and PCR Amplification

      Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

      ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

      gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

      Variant2: NM_000152.4:c.2024_2026delACA (p.Asn675del)

      ClinVar: 189006 https://www.ncbi.nlm.nih.gov/clinvar/variation/189006/

      gnomAD: East Asian 1.106e-4, Overall 8.275e-6 http://gnomad.broadinstitute.org/variant/17-78086806-CACA-C

      CaseAddInfo: One Pompe Mutation allele and One Pseudodeficency Mutation allele, 3 other people have this genotype

    1. 9

      Case9: 0.4 years diagnosis, Germany

      CasePresentingHPOs: HP:0001635, HP:0001252, HP:0001324, HP:0003236, HP:0001639 (Cardiac failure, Muscular hypotonia, Muscle weakness, Increased serum CK, Hypertrophic cardiomyopathy)

      HPOsFreeText: 18 BNP (pg/ml), 2.42 IVS (d) z score, 1.82 IVS (s) z score, Heart Failure at NYHA Class 1

      NotHPOsFreeText: No left-ventricular outflow tract obstruction

      CaseAddInfo: Infantile-Onset Pompe Disease

    1. 3.1 Description of the study population

      Patient1: IOPD Group, 25days old

      CasePresentingHPOs:

      HPOsFreeText: LDH = 480 U/L, CK = 1273 U/L, ALT = 52 U/L, AST = 102 U/L, Mann-Whitney Test = 3

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo:

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: NM_000152.4(GAA):c.2238G>C (p.Trp746Cys)

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

      gnomAD: 0.0003083, https://gnomad.broadinstitute.org/variant/17-78090815-G-C

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

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

      gnomAD: 0.000003988, https://gnomad.broadinstitute.org/variant/17-78090814-G-A

    1. 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

    2. 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. 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. 8

      Patient8: Female

      CasePresentingHPOs: HP:0004887, HP:0002194

      HPOsFreeText: ERT dosage = 20 mg/kg/2 w, able to sit independently, reversal of HCM, CRIM positive

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: Symptom onset, diagnosis, and ERT at 4mo, ERT last for 54mo, ventilation required at 60 mo, died at 60mo

      CasePMIDs: 14695532, 14972326

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: NM_000152.4(GAA):c.1064T>C (p.Leu355Pro)

      ClinVar: 284093, https://www.ncbi.nlm.nih.gov/clinvar/variation/284093/

      gnomAD: 8.304e-06, http://exac.broadinstitute.org/variant/17-78082197-T-C

    2. 10

      Patient10: Male

      CasePresentingHPOs: HP:0002194, HP:0001522

      HPOsFreeText: ERT dosage = 40 mg/kg/w, HCM reversal, CRIM positive

      CaseNotHPOs: HP:0004887

      NotHPOsFreeText:

      CaseAddInfo: Symptom onset at 3w, diagnosis at 3mo, ERT at 5mo, ERT lasted for 5mo, died at 12mo

      CasePMIDs: 22644586, 14695532

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

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

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

      gnomAD: 1.666e-05, http://exac.broadinstitute.org/variant/17-78079656-G-A

    3. 17

      Patient17: Female

      CasePresentingHPOs: HP:0004887, HP:0003819

      HPOsFreeText: ERT dosage = 20mg/kg/2w, able to sit, CRIM positive

      CaseNotHPOs:

      NotHPOsFreeText: no HCM reversal

      CaseAddInfo: Symptom onset at 3mo, diagnosis at 6mo, ERT at 10mo, ERT lasted for 6mo, required ventilation at 26mo, died at 28mo

      CasePMIDs: 22644586, 14695532

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

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

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

      gnomAD: 1.666e-05, http://exac.broadinstitute.org/variant/17-78079656-G-A

    4. 5

      Patient5: Female

      CasePresentingHPOs: HP:0004887, HP:0002194, HP:0001522

      HPOsFreeText: ERT dosage = 20 mg/kg/2 w, CRIM positive

      CaseNotHPOs:

      NotHPOsFreeText:

      CaseAddInfo: Symptom onset at 2mo, diagnosis and ERT at 4mo, ERT lasted for 1mo, ventilation required at 3mo, died at 5mo, variants in trans

      CasePMIDs: 21763167, 11738358

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant1: 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

      Variant2: NM_000152.4(GAA):c.1802C>T (p.Ser601Leu)

      ClinVar: 194154, https://www.ncbi.nlm.nih.gov/clinvar/variation/194154/

      gnomAD: 0.00003187, http://gnomad.broadinstitute.org/variant/17-78086424-C-T

    5. 13

      Patient13: Female

      CasePresentingHPOs:

      HPOsFreeText: ERT dosage = 20mg/kg/2w, HCM reversal, CRIM positive, able to run and climb stairs, can speak well

      CaseNotHPOs: HP:0004887, HP:0009046

      NotHPOsFreeText:

      CaseAddInfo: Symptom onset at 2mo, diagnosis at 6mo, ERT at 8mo, ERT lasted for 111mo, currently 10yo

      CasePMIDs: 14695532, 14972326

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

      Variant: NM_000152.4(GAA):c.1064T>C (p.Leu355Pro)

      ClinVar: 284093, https://www.ncbi.nlm.nih.gov/clinvar/variation/284093/

      gnomAD: 8.304e-06, http://exac.broadinstitute.org/variant/17-78082197-T-C

    1. 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. 1/F

      Patient1: Female, Caucasian, 10yo

      CasePresentingHPOs:

      HPOsFreeText: IOPD, rhGAA IgG antibody titer = 400, CRIM positive

      CaseNotHPOs:

      NotHPOsFreeText: no infusion associated reactions

      CaseAddInfo: homozygous, 6.5mo at diagnosis, 7.0mo at ERT start

      CasePMIDs:

      CasePreviousTesting: same as group

      CaseGenotypingMethod: same as group

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

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

      gnomAD: 0.00001809, https://gnomad.broadinstitute.org/variant/17-78079656-G-A

    1. 9

      Case#: Patient 9, Gender N/A, Onset at 3-4 months. Death around 1-2 years, Southeast Asian

      DiseaseAssertion: Pompe disease

      FamilyInfo: N/A

      CasePresentingHPOs: HP:0001252, HP:0001270, HP:0001640, HP:0005165

      Muscular hypotonia, Motor delay, Cardiomegaly, Shortened PR interval)

      CaseHPOFreeText: BVH, Ejection fraction 10%, Creatine kinase levels 1,010u/l

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CasePreviousTesting: No GAA measurement . Ejection fraction 10%, Creatine kinase levels 1,010u/l

      PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions

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

      ClinVar: 550327

      CAID: N/A

      gnomAD: Highes population MAF = 0.0001427 (Others)

      ParentalGenotype: Both parents were carriers for the viariant c.1941C>G (p.Cys647Trp)

      PreviouslyPublished: N/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. 4H-Sc.236C>T (p.A79V)c.1882C>T (p.R628*)This report

      Case#: Kwak Patient #4, 2yo at dx

      DiseaseAssertion: Hurler-Scheie

      FamilyInfo:

      CasePresentingHPOs: HP:0000280, HP:0007957, HP:0100790, HP:0000924, HP:0001627, HP:0001433

      CaseHPOFreeText: IDUA activity=6.5 nmol/mg protein/hr, uGAGs=202.8 CPC unit/g creatinine

      CaseNotHPOs:

      CaseNotHPOFreeText:

      PreviouslyPublished:

      Variant: c.236C>T (p.A79V); c.1882C>T (p.R628*)-Path in ClinVar

      ClinVar: 1458769; 550421

      CAID:

      SupplementalData: supplemental file contains phenotype information

  2. Nov 2026
    1. TTL Overexpression Rescues Hypertrophy in Cardiomyocytes Derived From an HCM hiPSC Line

      Case1: HCM patient-derived cell line UKEi070-A (demographics not reported in this paper) DiseaseAssertion: HCM

      ParentalTesting: CasePresentingHPOs: HP:0001639 CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CasePreviousTesting: Genotyping Method: Not reported in this paper; it references a previously established patient-derived cell line. FunctionalAnalysis: The variant is reported to cause MYBPC3 protein haploinsufficiency in cardiomyocytes. In this study, TTL overexpression normalized cell hypertrophy in the HCM cell model. Variant: NM_000256.3:c.2308G>A (heterozygous; the paper reports the splice consequence as p.Asp770Serfs98X) ClinVar: 36604 CAID: gnomAD: NR AdditionalInfo: The paper uses patient-derived induced pluripotent stem cell cardiomyocytes; it does not provide the patient’s age, sex, or pedigree.

    1. A 50-year-old male with a prior clinical diagnosis of hypertrophic cardiomyopathy presented with monomorphic ventricular tachycardia.

      Case1: 50 year old male DiseaseAssertion: HCM; hydroxychloroquine cardiotoxicity FamilyInfo: Six children undergoing predictive testing for the familial MYBPC3 variant; family history not reported ParentalTesting: CasePresentingHPOs: HP:0001639 CaseHPOFreeText: Monomorphic ventricular tachycardia, dyspnea, nausea, vomiting, biventricular hypertrophy, systolic dysfunction, cardiogenic shock CaseNotHPOs: CaseNotHPOFreeText: CasePreviousTesting: Prior CMR showed nonobstructive HCM; cardiomyopathy gene panel identified the variant Genotyping Method: Cardiomyopathy gene panel FunctionalAnalysis: Altered splicing with exon 30 skipping; authors describe a nonfunctional protein or premature stop codon Variant: c.3330+5G>C ClinVar: 42706 CAID: gnomAD: 0.03% (as reported in the article) AdditionalInfo: Long-term hydroxychloroquine exposure for malaria prophylaxis; biopsy findings were consistent with both HCM and hydroxychloroquine cardiotoxicity

    1. 3.1.2 Patient 2—heart transplanted DCM and intronic MYBPC3 variant

      Case2: 12-year-old boy (Patient 2) DiseaseAssertion: DCM FamilyInfo: Family history unremarkable. ParentalTesting: The MYBPC3 variant was inherited from his father. The father’s cardiac phenotype is not reported. CasePresentingHPOs: HP:0001644, HP:0003546 CaseHPOFreeText: Severely depressed biventricular function; heart transplantation for decompensated heart failure. CaseNotHPOs: CaseNotHPOFreeText: CasePreviousTesting: Previous WES was negative; the variant’s intronic region was not adequately covered. Genotyping Method: Whole-genome sequencing (WGS; Illumina NovaSeq 6000; aligned to hg19/GRCh37). FunctionalAnalysis: SpliceAI predicted a potential splicing effect; no functional assay in this patient is reported. Variant: NM_000256.3:c.1224-80G>A (heterozygous intronic variant) ClinVar: 693982 CAID: CA221697326 gnomAD: 0.0000637 AdditionalInfo: The authors classified the variant as a VUS in this DCM case because evidence for a MYBPC3–DCM relationship is limited. ClinVar currently reports a pathogenic/likely pathogenic aggregate classification, primarily in relation to HCM. Reanalysis found no second MYBPC3 variant.

  3. Oct 2026
    1. 203

      Case#: 203 6.1yrs male, age at initial diagnosis 4.9 yrs DiseaseAssertion: MPS IH-S FamilyInfo:Nil CasePresentingHPOs: CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: IDUA activity: low leukocyte IDUA enzyme activity CaseUrineGAGs: CaseERT: 1.7 yrs on ERT, then study drug, valanafusp alpha, also called AGT-181 for 12 months

      CaseBMT: No PreviouslyPublished Don't know Variant1:p.R621X Variant1ClinVarID: 11917 Variant1CAID: Variant2:IVS9-12_4delCAGGCCCCG . However the sequence at this location corresponds to "cccgccccg" Variant2ClinVarID: Variant2CAID:

    2. 211

      Case#: 211 2.5 yrs male, age at initial diagnosis 2.4 yrs DiseaseAssertion: MPS IH FamilyInfo:Nil CasePresentingHPOs: CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: IDUA activity: low leukocyte IDUA enzyme activity CaseUrineGAGs: CaseERT: Nil, study drug, valanafusp alpha, also called AGT-181 for 12 months

      CaseBMT: No PreviouslyPublished Don't know Variant1:p.G208D Variant1ClinVarID: 554590 Variant1CAID: Variant2:p.G208D Variant2ClinVarID: 554590 Variant2CAID:

    1. Case#: Patient D2, Druze religious group, located in lower Galilee.

      DiseaseAssertion: MPS1-H

      FamilyInfo: N/A

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CaseEnzymeAssay: N/A

      CaseUrineGAGs: N/A

      CaseERT: N/A

      CaseBMT: N/A

      Variant1: c.928C>T (p.Q310X)

      Variant1ClinVarID: 11915

      Variant1CAID: N/A

      Variant2: N/A

      Variant2ClinVarID: N/A

      Variant2CAID: N/A

      AdditionalVariants: N/A

      ParentalGenotype: N/A

      PreviouslyPublished N/A

    2. Case#: Patient D4, Druze religious group, located in lower Galilee.

      DiseaseAssertion: N/A

      FamilyInfo: May have relation with Patient D5 due to being located in the same village. Parents were found to be heterozygous for the mutation.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CaseEnzymeAssay: N/A

      CaseUrineGAGs: N/A

      CaseERT: N/A

      CaseBMT: N/A

      Variant1: c.1096A>C (p.T366P)

      Variant1ClinVarID: 11916

      Variant1CAID: CA:256117

      Variant2: N/A

      Variant2ClinVarID: N/A

      Variant2CAID: N/A

      AdditionalVariants: N/A

      ParentalGenotype: N/A

      PreviouslyPublished N/A

    3. Case#: Patient D5, Druze religious group, located in lower Galilee.

      DiseaseAssertion: N/A

      FamilyInfo: May have relation with Patient D5 due to being located in the same village. Parents were found to be heterozygous for the mutation.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CaseEnzymeAssay: N/A

      CaseUrineGAGs: N/A

      CaseERT: N/A

      CaseBMT: N/A

      Variant1: c.1096A>C (p.T366P)

      Variant1ClinVarID: 11916

      Variant1CAID: CA:256117

      Variant2: N/A

      Variant2ClinVarID: N/A

      Variant2CAID: N/A

      AdditionalVariants: N/A

      ParentalGenotype: N/A

      PreviouslyPublished N/A

    4. Case#: Patient M2, Muslim religious group, located in lower Galilee.

      DiseaseAssertion: MPS1-H

      FamilyInfo: Parents of M2 were found to be heterozygous for this mutation.

      CasePresentingHPOs: N/A

      CaseHPOFreeText: N/A

      CaseNotHPOs: N/A

      CaseNotHPOFreeText: N/A

      CaseEnzymeAssay: N/A

      CaseUrineGAGs: N/A

      CaseERT: N/A

      CaseBMT: N/A

      Variant1: c.1096A>C (p.T366P)

      Variant1ClinVarID: 11916

      Variant1CAID: CA:256117

      Variant2: N/A

      Variant2ClinVarID: N/A

      Variant2CAID: N/A

      AdditionalVariants: N/A

      ParentalGenotype: N/A

      PreviouslyPublished N/A

    1. In family B

      Case#: Patient 2 of family B: Female DiseaseAssertion:MPS1 FamilyInfo:Consanguinity Yes CasePresentingHPOs: NA CaseHPOFreeText: CaseNotHPOs: CaseNotHPOFreeText: CaseEnzymeAssay: enzyme values lower than the cut-off values CaseUrineGAGs: NA CaseERT: NA CaseBMT:Nil Variant1:c.1469T>C ,Leu490Pro Variant1ClinVar ID: 11919 Variant1CAID: Variant2:c.1469T>C ,Leu490Pro Variant2ClinVarID:11919 Variant2CAID: AdditionalVariants:Nil ParentalGenotype:NA PreviouslyPublishedNA

    1. three siblings

      Case#: Eldest child, female, age at diagnosis and onset are unknown, age at treatment is 6, age at report is 11 DiseaseAssertion: MPS1 FamilyInfo: All 3 cases are siblings CasePresentingHPOs: HP:0000280, HP:0008800, HP:0010501, HP:0006467, HP:0001659, HP:0001653, HP:0001634 (Coarse facial features, Limited hip movement, Limited shoulder movement, Limitation of knee mobility, Aortic regurgitation, Mitral regurgitation, Mitral valve prolapse) CaseHPOFreeText: Corneal clouding CaseNotHPOs: N/A CaseNotHPOFreeText: N/A CaseEnzymeAssay: N/A CaseUrineGAGs: N/A CaseERT: Yes CaseBMT: Don't know Variant1: p.Leu490Pro Variant1ClinVarID: 11919 Variant1CAID: Variant2: p.Leu490Pro Variant2ClinVarID: 11919 Variant2CAID: AdditionalVariants: N/A ParentalGenotype: N/A PreviouslyPublished N/A

    2. three siblings

      Case#: Youngest child, Female, age at diagnosis and onset are unknown, age at treatment is 4 months, age at report is 5 years, 4 months DiseaseAssertion: MPS1 FamilyInfo: All 3 cases are siblings CasePresentingHPOs: N/A CaseHPOFreeText: Mild corneal clouding, this study is to examine the efficacy of enzyme replacement therapy at different stages of teh disease, and it is assumed this patient is not yet old enough to have develped symptoms CaseNotHPOs: N/A CaseNotHPOFreeText: N/A CaseEnzymeAssay: N/A CaseUrineGAGs: N/A CaseERT: Yes CaseBMT: Don't know Variant1: p.Leu490Pro Variant1ClinVarID: 11919 Variant1CAID: Variant2: p.Leu490Pro Variant2ClinVarID: 11919 Variant2CAID: AdditionalVariants: N/A ParentalGenotype: N/A PreviouslyPublished N/A

    3. three siblings

      Case#: Middle child, Male, age at diagnosis and onset are unknown, age at treatment is 2.5 years, age at report is 7.5 years DiseaseAssertion: MPS1 FamilyInfo: All 3 cases are siblings CasePresentingHPOs: HP:0001634, HP:0001653 (mitral valve prolapse, mitral regurgitation) CaseHPOFreeText: Mild corneal clouding CaseNotHPOs: N/A CaseNotHPOFreeText: N/A CaseEnzymeAssay: N/A CaseUrineGAGs: N/A CaseERT: Yes CaseBMT: Don't know Variant1: p.Leu490Pro Variant1ClinVarID: 11919 Variant1CAID: Variant2: p.Leu490Pro Variant2ClinVarID: 11919 Variant2CAID: AdditionalVariants: N/A ParentalGenotype: N/A PreviouslyPublished N/A

    1. CasePT-104: United States

      CasePresentingHPOs: HP:0001639 (Hypertrophic cardiomyopathy)

      HPOsFreeText: N/A

      CaseNotHPOs: HP:0001650, HP:0001658 (Aortic valve stenosis, Myocardial infarction)

      NotHPOsFreeText: N/A

      CaseAddInfo:


      CaseGenotypingMethod: DNA was collected from the participants using blood samples. 18 genes suspected on contributing to HCM were targeted and sequenced. The variants were then located and filtered for pathogenicity.


      Variant: NM_000257.3:c.4399C>G (p.Leu1467Val)

      ClinVar: 43015 https://www.ncbi.nlm.nih.gov/clinvar/variation/43015/

      gnomAD: South Asian 1.111e-3, Overall 1.352e-4 https://gnomad.broadinstitute.org/variant/14-23886482-G-C

    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

    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

    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. 9

      Case9: Male, 40 years onset, 45 years diagnosis, 74 years report, France

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

      HPOsFreeText: Lost ambulation at 50 years, Started invasive ventilation at 67 years, Started ERT given every other week at a dose of 20 mg/kg at 70 years for 43 months, Peak Anti-rhGAA antibodies at 1:409,600, Time off ventilation stayed constant at 0 min, Total Motor Function Measure from 29 to 26, 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. 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

    3. 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

    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. 4

      Case4: 0.5 years diagnosis, Germany

      CasePresentingHPOs: HP:0031185, HP:0001635, HP:0001252, HP:0001324, HP:0003236, HP:0001639 (Increased NT-proBNP level, Cardiac failure, Muscular hypotonia, Muscle weakness, Increased serum CK, Hypertrophic cardiomyopathy)

      HPOsFreeText: 3924 BNP (pg/ml), 7.68 IVS (d) z score, 6.42 IVS (s) z score, Heart Failure at NYHA Class 3

      NotHPOsFreeText: No left-ventricular outflow tract obstruction

      CaseAddInfo: Infantile-Onset Pompe Disease

    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. 15

      Patient15: Male, 21 years report, 2 years onset

      CasePresentingHPOs: N/A

      HPOsFreeText: GAA activity 4.7% from a dried blood spot

      CaseNotHPOs: HP:0002098, HP:0001324, HP:0001640, HP:0002240 (Respiratory distress, Muscle weakness, Cardiomegaly, Hepatomegaly)

      NotHPOsFreeText: No wheelchair needed, Respiratory Assistance not needed

      CaseAddInfo: LOPD