Case#: 1, age 36, age 30 (report)

DiseaseAssertion: Pompe Disease

FamilyInfo: Family 1, no further information

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

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

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: single gene sequencing/analysis, 48.47 NaG/AaGIA, 89.61% inhibition of GAA; NaG/AaGIA above 40 and %INH above 87 are in the affected range

Variants:

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

ClinVar: 550327

Variant 2: Not reported

ParentalGenotypes: N/A

PreviouslyPublished: N/A

Case#: 2/b, age 11, age 5 (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, 105.01 NaG/AaGIA, 90.98% 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

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

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

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

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

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

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

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

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

CaseHPOFreeText:

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

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 935199

Variant 2 CAid: CA401369553

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

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

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

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

CaseHPOFreeText:

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

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 189040

Variant 2 CAid: CA274304

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

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

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

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

CaseHPOFreeText:

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

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 189065

Variant 2 CAid: CA274334

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 14, female, 58 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0001252 (Hypotonia)

CaseHPOFreeText:

CaseNotHPOs: HP:0003546 (Exercise intolerance), HP:0002094 (dyspnoea), HP:0001638 (cardiomyopathy), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002153 (hyperkalemia), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

glucosidase activity: GAA activity was 0.33 mol/Lh in dried blood spots (normal range >0.75).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 19, male, 63 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

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

CaseHPOFreeText:

CaseNotHPOs: HP:0001638 (cardiomyopathy), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

glucosidase activity: GAA activity was 0.47 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.2065G>A (p.Glu689Lys)

Variant 1 ClinVarID: 4030

Variant 1 CAid: CA116612

Variant 2: N/A

Variant 2 ClinVarID: N/A

Variant 2 CAid: N/A

Zygosity: Heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 17, male, 64 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

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

CaseHPOFreeText:

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

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

glucosidase activity: GAA activity was 0.54 mol/Lh in dried blood spots (normal range >0.75).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.875A>G (p.Tyr292Cys)

Variant 2 ClinVarID: 370577

Variant 2 CAid: CA16041886

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 12, male, 52 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText:

CaseNotHPOs: HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0001638 (cardiomyopathy), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002153 (hyperkalemia), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

glucosidase activity: GAA activity was 0.48 mol/Lh in dried blood spots (normal range >0.75).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1889-1G>A

Variant 2 ClinVarID: N/A

Variant 2 CAid: CA401369820

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 1, male, 0 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: Family member with PD

CasePresentingHPOs: HP:0001638 (cardiomyopathy)

CaseHPOFreeText:

CaseNotHPOs: HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: not asymptomatic, no biopsy

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

glucosidase activity: GAA activity was 0.5 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.236_246delCCACACAGTGC (p.Pro79ArgfsTer13)

Variant 1 ClinVarID: 371302

Variant 1 CAid: CA16041880

Variant 2: NM_000152.5(GAA):c.236_246delCCACACAGTGC (p.Pro79ArgfsTer13)

Variant 2 ClinVarID: 371302

Variant 2 CAid: CA16041880

Zygosity: homozygous

ParentalGenotype: "the clinical information refers to parents as carriers of the disease, but the genetic study of his parents was not sent to us."

PreviouslyPublished: N/A

Case#: Subject number 3, female, 9 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: Family member with PD

CasePresentingHPOs:

CaseHPOFreeText: Asymptomatic

CaseNotHPOs: HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea), HP:0001638 (cardiomyopathy)

CaseNotHPOFreeText: no biopsy

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

glucosidase activity: GAA activity was 0.15 mol/Lh in dried blood spots (normal range >0.75).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1396_1397insG (p.Val466GlyfsTer?)

Variant 2 ClinVarID: ?

Variant 2 CAid: CA627699396

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 16, male, 59 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0002153 (hyperkalemia), HP:0002098 (respiratory distress), HP:0001324 (muscle weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0001252 (Hypotonia), HP:0001638 (cardiomyopathy), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0003546 (Exercise intolerance), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

glucosidase activity: GAA activity was 0.17 mol/Lh in dried blood spots (normal range >0.75).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 10, male, 46 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia)

CaseHPOFreeText:

CaseNotHPOs: HP:0001638 (cardiomyopathy), HP:0002098 (respiratory distress), HP:0002153 (hyperkalemia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

glucosidase activity: GAA activity was 0.36 mol/Lh in dried blood spots (normal range >0.75).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.236_246delCCACACAGTGC (p.Pro79ArgfsTer13)

Variant 2 ClinVarID: 371302

Variant 2 CAid: CA16041880

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 8, female, 32 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

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

CaseHPOFreeText:

CaseNotHPOs: HP:0001638 (cardiomyopathy), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

glucosidase activity: GAA activity was 0.3 mol/Lh in dried blood spots (normal range >0.75).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.925G>A (p.Gly309Arg)

Variant 2 ClinVarID: 188797

Variant 2 CAid: CA273972

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 13, female, 57 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0002094 (dyspnoea)

CaseHPOFreeText:

CaseNotHPOs: HP:0001252 (Hypotonia), HP:0001638 (cardiomyopathy), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002153 (hyperkalemia), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

glucosidase activity: GAA activity was 0.37 mol/Lh in dried blood spots (normal range >0.75).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2237G>C (p.Trp746Ser)

Variant 2 ClinVarID: 188484

Variant 2 CAid: CA198797

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 2, female, 7 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: Family member with PD

CasePresentingHPOs:

CaseHPOFreeText: Asymptomatic

CaseNotHPOs: HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea), HP:0001638 (cardiomyopathy)

CaseNotHPOFreeText: no biopsy

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

glucosidase activity: GAA activity was 0.12 mol/Lh in dried blood spots (normal range >0.75).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1396_1397insG (p.Val466GlyfsTer?)

Variant 2 ClinVarID: ?

Variant 2 CAid: CA627699396

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 5, female, 17 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

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

CaseHPOFreeText: Biopsy

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

CaseNotHPOFreeText: not asymptomatic

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

glucosidase activity: GAA activity was 0.37 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.1328A>T (p.Asp443Val)

Variant 1 ClinVarID: N/A

Variant 1 CAid: CA401366199

Variant 2: NM_000152.5(GAA):c.1328A>T (p.Asp443Val)

Variant 2 ClinVarID: N/A

Variant 2 CAid: CA401366199

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 9, female, 44 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001638 (cardiomyopathy), HP:0002098 (respiratory distress)

CaseHPOFreeText:

CaseNotHPOs: HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

glucosidase activity: GAA activity was 0.34 mol/Lh in dried blood spots (normal range >0.75).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2819C>A (p.Ser940Ter)

Variant 2 ClinVarID: ?

Variant 2 CAid: CA401327757

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 18, female, 79 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: Family member with PD

CasePresentingHPOs:

CaseHPOFreeText: Asymptomatic

CaseNotHPOs: HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0001252 (Hypotonia), HP:0001638 (cardiomyopathy), HP:0002098 (respiratory distress), HP:0003546 (Exercise intolerance), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy

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

glucosidase activity: GAA activity was 0.65 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.854C>G (p.Pro285Arg)

Variant 1 ClinVarID: 225114

Variant 1 CAid: CA358045

Variant 2: N/A

Variant 2 ClinVarID: N/A

Variant 2 CAid: N/A

Zygosity: Heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 6, male, 19 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: Family member with PD

CasePresentingHPOs:

CaseHPOFreeText: Asymptomatic

CaseNotHPOs: HP:0001638 (cardiomyopathy), HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy

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

glucosidase activity: GAA activity was 0.37 mol/Lh in dried blood spots (normal range >0.75).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.281_282delCT (p.Pro94ArgfsTer?)

Variant 2 ClinVarID: 370458

Variant 2 CAid: CA16041881

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 7, male, 31 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

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

CaseHPOFreeText:

CaseNotHPOs: HP:0001638 (cardiomyopathy), HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

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

glucosidase activity: GAA activity was 0.27 mol/Lh in dried blood spots (normal range >0.75).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 279811

Variant 2 CAid: CA8815429

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Patient (case report), male, 1 month old, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: No history of consanguinity in parents. The patient has a 15 months old sibling that is healthy.

Family medical history was notable for tuberous sclerosis in the patient’s father’s first cousin.

CasePresentingHPOs: HP:0200128, HP:0001639, HP:0002240

(Biventricular hypertrophy, Hypertrophic cardiomyopathy, Hepatomegaly,

CaseHPOFreeText: Echogenic mass within the left ventricle.

Short-axis images revealed the possibility of an additional mass within the left ventricle adjacent to the papillary muscles

Right axis deviation

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

Normal results were noted for levels of plasma amino acids, lactate and pyruvate, total and free carnitine, and acylcarnitine compounds. Urine organic acid quantitation was normal.

PR interval was normal

CasePreviousTesting: The serum creatine kinase was elevated (478 U/L; normal 60–305 U/L).

GAA activity in whole blood from a blood spot was 1.8 pmol/punch/hour (control 10–49 pmol/punch/hour)

The GAA gene was sequenced.

Variant 1: NM_000152.5(GAA):c.525del (p.Glu176fs)

ClinVar: 4033

CAID: CA220406

gnomAD: N/A

Variant 2: NM_000152.5(GAA):c.1927G>A (p.Gly643Arg)

ClinVar: 4023

CAID: CA116596

gnomAD: Highest population MAF=0.00003667 (Euroean (non-Finnish))

ParentalGenotype:N/A

PreviouslyPublished:N/A

PMID: 23430912

Gene: GAA

Case#: Subject number 6(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

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

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 2(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 72 U/L (28-300 U/L is normal), AST: 21 U/L (24-72 U/L is normal), ALT: 23 U/L (17-63 U/L is normal), Hex4: 4.2 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 1.86 micromole/L/h and GAA activity #2 (NBS) 1.44 in dried blood spots (>2.10 micromole/L/h is normal). 5.3 in confirmatory testing (>6.7 is normal).

Variant 1: NM_000152.5(GAA):c.2238G>C

Variant 1 ClinVarID: 265160

Variant 1 CAid: CA8815665

Variant 2: NM_000152.5(GAA):c.1552-3C>G

Variant 2 ClinVarID: 419722

Variant 2 CAid: CA8815383

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 17(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 275 U/L (60-305 U/L is normal), AST: 150 U/L (22-71 U/L is normal), ALT: 42 U/L (7-50 U/L is normal), Hex4: 5.2 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP 44.5 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 1.04 micromole/L/h and GAA activity #2 (NBS) 0.77 in dried blood spots (>2.10 micromole/L/h is normal). 1.80 in confirmatory testing (>3.88 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 29(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

glucosidase activity: GAA activity #2 (NBS) 0.48 in dried blood spots (>2.10 micromole/L/h is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1547G>A

Variant 2 ClinVarID: 983721

Variant 2 CAid: CA401367155

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 28(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

glucosidase activity: GAA activity #2 (NBS) 1.06 in dried blood spots (>2.10 micromole/L/h is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2238G>C

Variant 2 ClinVarID: 265160

Variant 2 CAid: CA8815665

Variant 3: NM_000152.5(GAA):c.2065G>A

Variant 3 ClinVarID: 4030

Variant 3 CAid: CA116612

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 20(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 204 U/L (60-305 U/L is normal), AST: 63 U/L (22-71 U/L is normal), ALT: 34 U/L (7-50 U/L is normal), BNP 65.4 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 0.88 micromole/L/h and GAA activity #2 (NBS) 0.77 in dried blood spots (>2.10 micromole/L/h is normal). 3.50 in confirmatory testing (>3.88 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 26(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

glucosidase activity: GAA activity #2 (NBS) 1.01 in dried blood spots (>2.10 micromole/L/h is normal).

Variant 1: NM_000152.5(GAA):c.2238G>C

Variant 1 ClinVarID: 265160

Variant 1 CAid: CA8815665

Variant 2: NM_000152.5(GAA):c.2238G>C

Variant 2 ClinVarID: 265160

Variant 2 CAid: CA8815665

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 14(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 467 U/L (60-305 U/L is normal), AST: 166 U/L (20-64 U/L is normal), ALT: 73 U/L (12-42 U/L is normal), Hex4: 7.0 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 1.68 micromole/L/h and GAA activity #2 (NBS) 0.79 in dried blood spots (>2.10 micromole/L/h is normal). 2.40 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.156_157delTC

Variant 1 ClinVarID: N/A

Variant 1 CAid: CA294886619

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 1(I), male, 21 days (start of ERT), 31 months (report)

DiseaseAssertion: Infantile Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002870 (obstructive sleep apnea), HP:0001639 (hypertrophic cardiomyopathy), HP:0200128 (biventricular hypertrophy), HP:0030234 (Highly elevated creatine kinase)

CaseHPOFreeText: moderately to severely decreased left ventricular systolic wall motion, moderate hypertrophy of the left ventricle, severe right ventricular hypertrophy, requires BiPAP at night, patient receives physical, occupational, and speech therapies.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 923 U/L (60–305 U/L is normal), AST: 103 U/L (30–100 U/L is normal), BNP: 1080 pg/mL (0.0–100.0 pg/mL), Hex4: 24.7 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 0.65 micromole/L/h and GAA activity #2 (NBS) 0.22 in dried blood spots (>2.10 micromole/L/h is normal). 4.4 in confirmatory testing (>6.7 is normal).

Variant 1: NM_000152.5(GAA):c.759delC

Variant 1 ClinVarID: 837937

Variant 1 CAid: CA916082438

Variant 2: NM_000152.5(GAA):c.1551+1G>C

Variant 2 ClinVarID: 554983

Variant 2 CAid: CA401367167

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 22(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 265 U/L (60-305 U/L is normal), AST: 92 U/L (22-71 U/L is normal), ALT: 46 U/L (7-50 U/L is normal), Hex4: 5.9 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP 81.5 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 1.07 micromole/L/h and GAA activity #2 (NBS) 0.92 in dried blood spots (>2.10 micromole/L/h is normal). 1.60 in confirmatory testing (>3.88 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 2(I), male, 10 days (start of ERT)

DiseaseAssertion: Infantile Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0200128 (biventricular hypertrophy), HP:0005165 (shortened PR interval), HP:0030234 (Highly elevated creatine kinase), HP:0001270 (motor delay)

CaseHPOFreeText: severe septal left ventricular hypertrophy and mildly hypertrophied right ventricle. CRIM positive.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 846 U/L (60–305 U/L is normal), AST: 189 U/L (30–100 U/L is normal), ALT: 91 U/L (7-50 U/L is normal), BNP: 1232.5 pg/mL (0.0–100.0 pg/mL), Hex4: 30.2 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 0.65 micromole/L/h and GAA activity #2 (NBS) 0.34 in dried blood spots (>2.10 micromole/L/h is normal). 0.4 in confirmatory testing (<3.88 is normal).

Variant 1: NM_000152.5(GAA):c.525delT

Variant 1 ClinVarID: 4033

Variant 1 CAid: CA220406

Variant 2: NM_000152.5(GAA):c.1694_1697delTCTC

Variant 2 ClinVarID: N/A

Variant 2 CAid: CA658795263

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 25(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

glucosidase activity: GAA activity #2 (NBS) 0.95 in dried blood spots (>2.10 micromole/L/h is normal).

Variant 1: NM_000152.5(GAA):c.2238G>C

Variant 1 ClinVarID: 265160

Variant 1 CAid: CA8815665

Variant 2: NM_000152.5(GAA):c.2238G>C

Variant 2 ClinVarID: 265160

Variant 2 CAid: CA8815665

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 7(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 283 U/L (30-135 U/L is normal), Hex4: 2.6 mmol/mol Creatinine (≤3.0 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 1.05 micromole/L/h and GAA activity #2 (NBS) 0.19 in dried blood spots (>2.10 micromole/L/h is normal). 2.2 in confirmatory testing (>3.88 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.546 G>A

Variant 2 ClinVarID: 280955

Variant 2 CAid: CA8814895

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 23(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 48 U/L (60-305 U/L is normal), AST: 73 U/L (22-71 U/L is normal), ALT: 28 U/L (7-50 U/L is normal), BNP 102.3 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 1.12 micromole/L/h and GAA activity #2 (NBS) 0.62 in dried blood spots (>2.10 micromole/L/h is normal). 2.5 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.2238G>C

Variant 1 ClinVarID: 265160

Variant 1 CAid: CA8815665

Variant 2: NM_000152.5(GAA):c.2238G>C

Variant 2 ClinVarID: 265160

Variant 2 CAid: CA8815665

Variant 3: NM_000152.5(GAA):c.2065G>A

Variant 3 ClinVarID: 4030

Variant 3 CAid: CA116612

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 11(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 421 U/L (60-305 U/L is normal)

glucosidase activity: GAA activity (NBS) 0.63 in dried blood spots (>2.10 micromole/L/h is normal). 3.00 in confirmatory testing (>3.88 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2560C>T

Variant 2 ClinVarID: 4034

Variant 2 CAid: CA340130

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 13(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 122 U/L (60-305 U/L is normal), AST: 78 U/L (20-64 U/L is normal), ALT: 42 U/L (12-42 U/L is normal), Hex4: 4.8 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP 71.8 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 0.56 micromole/L/h and GAA activity #2 (NBS) 0.62 in dried blood spots (>2.10 micromole/L/h is normal). 3.80 in confirmatory testing (>3.88 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 5(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 333 U/L (28-300 U/L is normal), AST: 52 U/L (24-72 U/L is normal), ALT: 46 U/L (17-63 U/L is normal), Hex4: 4.4 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 1.82 micromole/L/h and GAA activity #2 (NBS) 0.94 in dried blood spots (>2.10 micromole/L/h is normal). 6.9 in confirmatory testing (>6.7 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 4(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 361 U/L (28-300 U/L is normal), AST: 66 U/L (24-72 U/L is normal), ALT: 52 U/L (17-63 U/L is normal), Hex4: 3.9 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 1.24 micromole/L/h and GAA activity #2 (NBS) 0.67 in dried blood spots (>2.10 micromole/L/h is normal). 2.4 in confirmatory testing (>6.7 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 27(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 108 U/L (60-305 U/L is normal), AST: 32 U/L (22-71 U/L is normal), ALT: 29 U/L (7-50 U/L is normal), Hex4: 3.3 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP 35.7 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 (NBS) is 1.1 micromole/L/h and GAA activity #2 (NBS) 0.42 in dried blood spots (>2.10 micromole/L/h is normal). 2.40 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.1441T>C

Variant 1 ClinVarID: 189007

Variant 1 CAid: CA274247

Variant 2: NM_000152.5(GAA):c.2238G>C

Variant 2 ClinVarID: 265160

Variant 2 CAid: CA8815665

Variant 3: NM_000152.5(GAA):c.2065G>A

Variant 3 ClinVarID: 4030

Variant 3 CAid: CA116612

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 15(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 68 U/L (60-305 U/L is normal), AST: 49 U/L (20-64 U/L is normal), ALT: 27 U/L (12-42 U/L is normal), Hex4: 2.8 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 1.11 micromole/L/h and GAA activity #2 (NBS) 0.5 in dried blood spots (>2.10 micromole/L/h is normal). 1.60 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.2238G>C

Variant 1 ClinVarID: 265160

Variant 1 CAid: CA8815665

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Variant 3: NM_000152.5(GAA):c.2065G>A

Variant 3 ClinVarID: 4030

Variant 3 CAid: CA116612

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 24(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 197 U/L (60-305 U/L is normal)

glucosidase activity: GAA activity #2 (NBS) 0.43 in dried blood spots (>2.10 micromole/L/h is normal).

Variant 1: NM_000152.5(GAA):c.1856G>A

Variant 1 ClinVarID: 370146

Variant 1 CAid: CA8815500

Variant 2: NM_000152.5(GAA):c.2238G>C

Variant 2 ClinVarID: 265160

Variant 2 CAid: CA8815665

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 21(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 155 U/L (60-305 U/L is normal), AST: 71 U/L (22-71 U/L is normal), ALT: 60 U/L (7-50 U/L is normal), Hex4 12.6 mmol/mol Creatine (≤20 is normal)

glucosidase activity: GAA activity #1 was 1.77 micromole/L/h and GAA activity #2 (NBS) 0.84 in dried blood spots (>2.10 micromole/L/h is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 19(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 510 U/L (60-305 U/L is normal), AST: 158 U/L (22-71 U/L is normal), ALT: 39 U/L (7-50 U/L is normal), Hex4: 8.1 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP <10.0 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 1.07 micromole/L/h and GAA activity #2 (NBS) 0.38 in dried blood spots (>2.10 micromole/L/h is normal). 1.10 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.456_458insGA

Variant 1 ClinVarID: ?

Variant 1 CAid: ?

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 18(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 542 U/L (60-305 U/L is normal), AST: 152 U/L (22-71 U/L is normal), ALT: 55 U/L (7-50 U/L is normal), Hex4: 7.6 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP 16.5 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 0.7 micromole/L/h and GAA activity #2 (NBS) 0.34 in dried blood spots (>2.10 micromole/L/h is normal). 1.40 in confirmatory testing (>3.88 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2560C>T

Variant 2 ClinVarID: 4034

Variant 2 CAid: CA340130

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 9(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 145 U/L (60-305 U/L is normal), AST: 72 U/L (22-71 U/L is normal), ALT: 43 U/L (7-50 U/L is normal), Hex4: 5.3 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP 13.0 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 0.97 micromole/L/h and GAA activity #2 (NBS) 0.33 in dried blood spots (>2.10 micromole/L/h is normal). 0.93 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.2238G>C

Variant 1 ClinVarID: 265160

Variant 1 CAid: CA8815665

Variant 2: NM_000152.5(GAA):c.2281delGinsAT

Variant 2 ClinVarID: 370993

Variant 2 CAid: CA16041905

Variant 3: NM_000152.5(GAA):c.2065G>A

Variant 3 ClinVarID: 4030

Variant 3 CAid: CA116612

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 31(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

glucosidase activity: GAA activity #2 (NBS) 0.94 in dried blood spots (>2.10 micromole/L/h is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2238G>C

Variant 2 ClinVarID: 265160

Variant 2 CAid: CA8815665

Variant 3: NM_000152.5(GAA):c.2065G>A

Variant 3 ClinVarID: 4030

Variant 3 CAid: CA116612

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 10(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 617 U/L (60-305 U/L is normal), Hex4: 6.6 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 0.84 micromole/L/h and GAA activity #2 (NBS) 0.49 in dried blood spots (>2.10 micromole/L/h is normal). 2.1 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.1438-1G>C

Variant 1 ClinVarID: 189184

Variant 1 CAid: CA274472

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 30(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

glucosidase activity: GAA activity #2 (NBS) 1.07 in dried blood spots (>2.10 micromole/L/h is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 12(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 464 U/L (60-305 U/L is normal)

glucosidase activity: 2.60 in confirmatory testing (>3.88 is normal). AST: 112 (22–71); ALT: 50 (7–50)

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2238G>C

Variant 2 ClinVarID: 265160

Variant 2 CAid: CA8815665

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 3(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 125 U/L (28-300 U/L is normal), AST: 56 U/L (24-72 U/L is normal), ALT: 49 U/L (17-63 U/L is normal), Hex4: 4.5 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 1.73 micromole/L/h and GAA activity #2 (NBS) 1.08 in dried blood spots (>2.10 micromole/L/h is normal). 3.6 in confirmatory testing (>6.7 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 16(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 140 U/L (60-305 U/L is normal), AST: 73 U/L (22-71 U/L is normal), ALT: 39 U/L (7-50 U/L is normal), Hex4: 8.5 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP 99.8 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 1.06 micromole/L/h and GAA activity #2 (NBS) 0.26 in dried blood spots (>2.10 micromole/L/h is normal). 6.4 in confirmatory testing (>3.88 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 8(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 365 U/L (60-305 U/L is normal), Hex4: 5.23 mmol/mol Creatinine (≤8.9 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 0.83 micromole/L/h and GAA activity #2 (NBS) 0.85 in dried blood spots (>2.10 micromole/L/h is normal). 0.93 in confirmatory testing (>3.88 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 279811

Variant 2 CAid: CA8815429

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 1(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 530 U/L (28-300 U/L is normal), AST: 72 U/L (24-72 U/L is normal), ALT: 41 U/L (17-63 U/L is normal), Hex4: 4.9 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 1.86 micromole/L/h and GAA activity #2 (NBS) 0.78 in dried blood spots (>2.10 micromole/L/h is normal). 3.1 in confirmatory testing (>6.7 is normal).

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 7, male, 62 years (diagnosis), 66 years (baseline visit), 67 years (ERT), 67 years (ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 2, female, 20 years (diagnosis), 48 years (baseline visit), 39 years (ERT), 34 years (ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 30, male, 12 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)

CaseHPOFreeText:

CaseNotHPOs: HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress), HP:0001324 (Muscle Weakness)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 5, female, 20 years (diagnosis), 45 years (baseline visit), 42 years (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 4, female, 56 years (diagnosis), 63 years (baseline visit), 59 years (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 25, male, 41 years (diagnosis), 46 years (baseline visit), 43 years (ERT), 43 (age at ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 36, male, 44 years (diagnosis), 49 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)

CaseHPOFreeText:

CaseNotHPOs: HP:0002098 (respiratory distress), HP:0002870 (obstructive sleep apnea), HP:0001324 (Muscle Weakness)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 3, female, 26 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)

CaseHPOFreeText:

CaseNotHPOs: HP:0002870 (obstructive sleep apnea), HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 32, male, 39 years (diagnosis), 43 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0002098 (respiratory distress), HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 14, male, 41 years (diagnosis), 51 years (baseline visit), 45 years (ERT), 50 (ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 9, female, 29 years (diagnosis), 55 years (baseline visit), 48 years (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

PMID: 33732206

Gene: GAA

Disease: Pompe disease

Inheritance: Autosomal recessive

Case#: Subject number 35, female, 35 years (diagnosis), 35 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)

CaseHPOFreeText:

CaseNotHPOs: HP:0002098 (respiratory distress), HP:0002870 (obstructive sleep apnea), HP:0001324 (Muscle Weakness)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 18, female, 40 years (diagnosis), 65 years (baseline visit), 64 years (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 13, male, 43 years (diagnosis), 47 years (baseline visit), 45 years (ERT), 44 (ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 21, female, 20 years (diagnosis), 52 years (baseline visit), 45 years (ERT), 39 (age at ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 8, female, 49 years (diagnosis), 59 years (baseline visit), 52 years (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 1, female, 38 years (diagnosis), 50 years (baseline visit), 47 years (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002098 (respiratory distress), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText: No mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 31, male, 49 years (diagnosis), 51 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseHPOFreeText:

CaseNotHPOs: HP:0002098 (respiratory distress), HP:0001324 (Muscle Weakness)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 10, male, 13 years (diagnosis), 42 years (baseline visit), 39 years (ERT), 38 (ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 19, female, 24 years (diagnosis), 35 years (baseline visit), 29 years (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 34, female, 28 years (diagnosis), 39 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0002098 (respiratory distress), HP:0002870 (obstructive sleep apnea), HP:0003236 (Elevated circulating creatine kinase concentration)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 17, male, 14 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)

CaseHPOFreeText:

CaseNotHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 22, male, 47 years (diagnosis), 64 years (baseline visit), 57 years (ERT), 56 (age at ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 16, male, 22 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)

CaseHPOFreeText:

CaseNotHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 6, female, 36 years (diagnosis), 51 years (baseline visit), 47 years (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 28, male, 20 years (diagnosis), 43 years (baseline visit), 43 (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 23, male, 2 years (diagnosis), 8 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)

CaseHPOFreeText:

CaseNotHPOs: HP:0002870 (obstructive sleep apnea), HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 33, female, 16 years (diagnosis), 20 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)

CaseHPOFreeText:

CaseNotHPOs: HP:0002098 (respiratory distress), HP:0002870 (obstructive sleep apnea), HP:0001324 (Muscle Weakness)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 20, female, 29 years (diagnosis), 40 years (baseline visit), 40 years (ERT), 39 (age at ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 26, male, 35 years (diagnosis), 51 years (baseline visit), 51 years (ERT), 49 (age at ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 15, female, 35 years (diagnosis), 51 years (baseline visit), 46 years (ERT), 46 (ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 24, female, 42 years (diagnosis), 57 years (baseline visit), 55 years (ERT), 54 (age at ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 27, male, 35 years (diagnosis), 51 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 11, male, 23 years (diagnosis), 31 years (baseline visit), 24 years (ERT), 23 (ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 12, female, 20 years (diagnosis), 46 years (baseline visit), 39 years (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 29, female, 40 years (diagnosis), 54 years (baseline visit), 48 (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

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

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

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

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

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

CaseNotHPOFreeText: no infusion reaction, no tracheostomy

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: N/A

Variant 2 CAid: CA401366794

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 1, male, 22 years (report), 9 years (onset), 11 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002650, HP:0001638 (Scoliosis, cardiomyopathy)

CaseHPOFreeText: on BiPap, ambulatory

CaseNotHPOs: HP:0002617, HP:0000365, HP:0000360, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0000821 (aneurysm, hearing loss, tinnitus, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, hypothyroidism)

CaseNotHPOFreeText: No infusion reaction, no tracheostomy

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

Variant 1: NM_000152.5(GAA):c.1655T>C (p.Leu552Pro)

Variant 1 ClinVarID:279811

Variant 1 CAid:CA8815429

Variant 1 gnomAD MAF: 0.00007053; 8/113426 (European non-Finnish)[https://gnomad.broadinstitute.org/variant/17-78085800-T-C?dataset=gnomad_r2_1]

Variant 2: NM_000152.5(GAA):c.2238G>C (p.Trp746Cys)

Variant 2 ClinVarID:265160

Variant 2 CAid:CA9301331

Variant 2 gnomAD MAF: 0.0005673; 73/128684 (European non-Finnish)[https://gnomad.broadinstitute.org/variant/17-78090815-G-C?dataset=gnomad_r2_1]

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 7, male, 50 years (report), 32 years (onset), 38 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000365 (hearing loss)

CaseHPOFreeText: on BiPAP, ambulatory

CaseNotHPOs: HP:0002650, HP:0000360, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0000821, HP:0001638 (scoliosis, tinnitus, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, hypothyroidism, cardiomyopathy)

CaseNotHPOFreeText: No infusion reaction, no tracheostomy

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.925G>A (p.Gly309Arg)

Variant 2 ClinVarID: 188797

Variant 2 CAid: CA273972

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 4, male, 34 years (report), 5 years (onset), 30 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002650 (scoliosis)

CaseHPOFreeText: on BiPAP, ambulatory

CaseNotHPOs: HP:0000360, HP:0000365, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0000821, HP:0001638 (tinnitus, hearing loss, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, hypothyroidism, cardiomyopathy)

CaseNotHPOFreeText: No infusion reaction, no tracheostomy

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.258dupC (p.Asn87GlnfsTer9)

Variant 2 ClinVarID: 282842

Variant 2 CAid: CA8814826

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 11, male, 68 years (report), 30s years (onset), 55 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000360 (tinnitus), HP:0002650 (scoliosis), HP:0000939 (osteoporosis), HP:0000821 (hypothyroidism)

CaseHPOFreeText: on BiPAP, ambulatory, assistive device (walker, cane)

CaseNotHPOs: HP:0000365, HP:0002617, HP:0009830, HP:0100647, HP:0010788, HP:0001638 (hearing loss, aneurysm, peripheral neuropathy, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1951_1952delGGinsT (p.Gly651SerfsTer?)

Variant 2 ClinVarID: 633225

Variant 2 CAid: CA913191010

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 13, male, 50 years (report), 42 years (onset), 45 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

*CasePresentingHPOs:* HP:0000360 (tinnitus), HP:0002650 (scoliosis), HP:0001638 (cardiomyopathy), HP:0001638 (Graves disease), HP:0010788 (testicular cancer), HP:0000821 (hypothyroidism)

CaseHPOFreeText: on BiPAP, ambulatory

CaseNotHPOs: HP:0009830, HP:0000939, HP:0000365, HP:0002617 (peripheral neuropathy, osteoporosis, hearing loss, aneurysm)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.525_526delTG (p.Asn177ProfsTer11)

Variant 2 ClinVarID: 189057

Variant 2 CAid: CA274328

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 12, male, 63 years (report), 35 years (onset), 55 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0009830 (peripheral neuropathy)

CaseHPOFreeText: ambulatory, assistive device (cane, wheelchair)

CaseNotHPOs: HP:0000360, HP:0002650, HP:0000939, HP:0000821, HP:0000365, HP:0002617, HP:0100647, HP:0010788, HP:0001638 (tinnitus, scoliosis, osteoporosis, hypothyroidism, hearing loss, aneurysm, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy, not on BiPAP

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1951_1952delGGinsT (p.Gly651SerfsTer?)

Variant 2 ClinVarID: 633225

Variant 2 CAid: CA913191010

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

PMID: 31392188

Gene: GAA

Disease: Pompe disease

Inheritance: Autosomal recessive

Case#: Subject number 10, male, 70 years (report), 58 years (onset), 65 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000365 (hearing loss)

CaseHPOFreeText: on BiPAP, ambulatory, assistive device (walking stick occasionally)

CaseNotHPOs: HP:0000360, HP:0000821, HP:0002650, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0001638 (tinnitus, hypothyroidism, scoliosis, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2655_2656delCG (p.Val886GlufsTer2)

Variant 2 ClinVarID: 597005

Variant 2 CAid: CA913191011

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 18, male, 65 years (report), 40 years (onset), 62 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000365 (hearing loss), HP:0000939 (osteoporosis), HP:0001638 (cardiomyopathy)

CaseHPOFreeText: ambulatory, on BiPAP

CaseNotHPOs: HP:0000360, HP:0000821, HP:0002650, HP:0002617, HP:0009830, HP:0100647, HP:0010788 (tinnitus, hypothyroidism, scoliosis, aneurysm, peripheral neuropathy, Graves disease, Testicular cancer)

CaseNotHPOFreeText: no tracheostomy, no infusion reaction

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1051delG

Variant 2 ClinVarID: 188841

Variant 2 CAid: CA274024

Zygosity: Compound heterozygous

ParentalGenotype: N/A

Case#: Subject number 6, female, 57 years (report), 20s years (onset), 31 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002650 (scoliosis)

CaseHPOFreeText: on BiPAP, ambulatory, assistive device (walker)

CaseNotHPOs: HP:0000360, HP:0000365, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0000821, HP:0001638 (tinnitus, hearing loss, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, hypothyroidism, cardiomyopathy)

CaseNotHPOFreeText: No infusion reaction, no tracheostomy

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.925G>A (p.Gly309Arg)

Variant 2 ClinVarID: 188797

Variant 2 CAid: CA273972

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 2, male, 48 years (report), 39 years (onset), 43 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002617 (aneurysm)

CaseHPOFreeText: on BiPap, ambulatory

CaseNotHPOs: HP:0000365, HP:0000360, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0000821, HP:0002650, HP:0001638 (hearing loss, tinnitus, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, hypothyroidism, scoliosis, cardiomyopathy)

CaseNotHPOFreeText: No infusion reaction, no tracheostomy

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

Case#: Subject number 17, female, 33 years (report), 14 years (onset), 24 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000360 (tinnitus)

CaseHPOFreeText: ambulatory

CaseNotHPOs: HP:0009830, HP:0002650, HP:0000939, HP:0000821, HP:0000365, HP:0002617, HP:0100647, HP:0010788, HP:0001638 (peripheral neuropathy, scoliosis, osteoporosis, hypothyroidism, hearing loss, aneurysm, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy, not on BiPAP

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

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

Variant 2 ClinVarID: 189040

Variant 2 CAid: CA274304

Zygosity: Compound heterozygous

ParentalGenotype: N/A

Case#: Subject number 3, male, 56 years (report), 30s years (onset), 48 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A ** CasePresentingHPOs**: HP:0000365 (hearing loss), HP:0000360 (tinnitus)

CaseHPOFreeText: ambulatory

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

CaseNotHPOFreeText: No infusion reaction, no tracheostomy, not on BiPAP

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2431delC (p.Leu811TrpfsTer?)

Variant 2 ClinVarID: N/A

Variant 2 CAid: CA628018649

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 16, male, 64 years (report), 56 years (onset), 60 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs:

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

CaseNotHPOs: HP:0009830, HP:0000360, HP:0002650, HP:0000939, HP:0000821, HP:0000365, HP:0002617, HP:0100647, HP:0010788, HP:0001638 (peripheral neuropathy, tinnitus, scoliosis, osteoporosis, hypothyroidism, hearing loss, aneurysm, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.307T>G

Variant 2 ClinVarID: 92483

Variant 2 CAid: CA220404

Zygosity: Compound heterozygous

ParentalGenotype: N/A

Case#: Subject number 8, female, 49 years (report), 20s years (onset), 42 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000821 (hypothyroidism)

CaseHPOFreeText: ambulatory, assistive device (quad cane, wheelchair)

CaseNotHPOs: HP:0000365, HP:0002650, HP:0000360, HP:0002617, HP:0000939, HP:0009830, HP:0100647, HP:0010788, HP:0001638 (hearing loss, scoliosis, tinnitus, aneurysm, osteoporosis, peripheral neuropathy, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: No infusion reaction, no tracheostomy, not on BiPAP

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1437+2T>C

Variant 2 ClinVarID: 849313

Variant 2 CAid: CA401366685

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 5, male, 59 years (report), 10 years (onset), 33 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0000365 (hearing loss), HP:0000360 (tinnitus), HP:0000939 (osteoporosis)

CaseHPOFreeText: Tracheostomy, assistive device (wheelchair)

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

CaseNotHPOFreeText: No infusion reaction, no ambulatory, not on BiPAP

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.925G>A (p.Gly309Arg)

Variant 2 ClinVarID: 188797

Variant 2 CAid: CA273972

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 15, male, 42 years (report), 15 years (onset), 23 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs:

CaseHPOFreeText: on BiPAP, ambulatory

CaseNotHPOs: HP:0009830, HP:0000360, HP:0002650, HP:0000939, HP:0000821, HP:0000365, HP:0002617, HP:0100647, HP:0010788, HP:0001638 (peripheral neuropathy, tinnitus, scoliosis, osteoporosis, hypothyroidism, hearing loss, aneurysm, Graves disease, Testicular cancer, cardiomyopathy)

CaseNotHPOFreeText: no infusion reaction, no tracheostomy

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1134C>G

Variant 2 ClinVarID: 595469

Variant 2 CAid: CA401365023

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 9, female, 74 years (report), 30s years (onset), 62 years (diagnosis)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

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

CaseHPOFreeText: Infusion reaction, ambulatory, assistive device (cane for long distance)

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

CaseNotHPOFreeText: no tracheostomy, not on BiPAP

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

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

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2655_2656delCG (p.Val886GlufsTer2)

Variant 2 ClinVarID: 597005

Variant 2 CAid: CA913191011

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

PMID: 31256280

Gene: GAA

Disease: Pompe Disease

Inheritance: Autosomal Recessive

PMID: 30832705 Gene: GAA

Case#: Subject number 4, male, 5 months (onset), 34 months (first admission)

DiseaseAssertion: Pompe disease

FamilyInfo: "no family history of neuromuscular disorders"

CasePresentingHPOs: HP:0001712 (left ventricular hypertrophy), HP:0002194 (delayed gross motor development), HP:0004887 (respiratory failure requiring assisted ventilation), HP:0002090 (pneumonia), HP:0002205 (recurrent respiratory infections), HP:0003819 (death in childhood)

CaseHPOFreeText: ambulatory (transport ventilator), infantile-onset

CaseNotHPOs:

CaseNotHPOFreeText: no tracheostomy, no dysphagia at baseline, not on BiPAP

CasePreviousTesting: “GAA activity in peripheral blood leukocytes lower than normal”; on enzyme replacement therapy

Case#: Subject number 5, male, 1 month (onset), 3 months (first admission)

DiseaseAssertion: Pompe disease

FamilyInfo: "no family history of neuromuscular disorders"

CasePresentingHPOs: HP:0001714 (ventricular hypertrophy), HP:0002194 (delayed gross motor development), HP:0004887 (respiratory failure requiring assisted ventilation), HP:0002205 (recurrent respiratory infections), HP:0002090 (pneumonia)

CaseHPOFreeText: infantile-onset, dysphagia at baseline, on BiPAP

CaseNotHPOs:

CaseNotHPOFreeText: no tracheostomy

CasePreviousTesting: “GAA activity in peripheral blood leukocytes lower than normal”; on enzyme replacement therapy

Case#: Subject number 3, female, 47 months (onset), 49 months (first admission)

DiseaseAssertion: Pompe disease

FamilyInfo: Patients 2 and 3 are full siblings

CasePresentingHPOs: HP:0012378 (fatigue), HP:0009046 (difficulty running), HP:0001609 (hoarse voice), HP:0000508 (ptosis), HP:0004887 (respiratory failure requiring assisted ventilation)

CaseHPOFreeText: ambulatory (transport ventilator), juvenile-onset

CaseNotHPOs:

CaseNotHPOFreeText: no tracheostomy, no dysphagia at baseline, not on BiPAP

CasePreviousTesting: “GAA activity in peripheral blood leukocytes lower than normal”; on enzyme replacement therapy

Case#: Subject number 1, female, 15 months (onset), 32 months (first admission)

DiseaseAssertion: Pompe disease

FamilyInfo: "no family history of neuromuscular disorders"

CasePresentingHPOs: HP:0002355 (difficulty walking), HP:0002205 (recurrent respiratory infections), HP:0002747 (respiratory insufficiency due to muscle weakness), HP:0004887 (respiratory failure requiring assisted ventilation)

CaseHPOFreeText: Tracheostomy, on BiPAP, ambulatory (transport ventilator), juvenile-onset, assistive device (wheelchair)

CaseNotHPOs:

CaseNotHPOFreeText: no dysphagia at baseline

CasePreviousTesting: “GAA activity in peripheral blood leukocytes lower than normal”; on enzyme replacement therapy

Case#: Subject number 6, male, 4 months (onset), 4 months (first admission)

DiseaseAssertion: Pompe disease

FamilyInfo: "no family history of neuromuscular disorders"

CasePresentingHPOs: HP:0004887 (respiratory failure requiring assisted ventilation), HP:0001639 (hypertrophic cardiomyopathy), HP:0001522 (death in infancy), HP:0002090 (pneumonia)

CaseHPOFreeText: infantile-onset, dysphagia at baseline

CaseNotHPOs:

CaseNotHPOFreeText: no tracheostomy, not on BiPAP

CasePreviousTesting: “GAA activity in peripheral blood leukocytes lower than normal”; on enzyme replacement therapy

Case#: Subject number 2, male, 20 months (onset), 24 months (first admission)

DiseaseAssertion: Pompe disease

FamilyInfo: Patients 2 and 3 are full siblings

CasePresentingHPOs: HP:0002355 (difficulty walking), HP:0002205 (recurrent respiratory infections), HP:0004887 (respiratory failure requiring assisted ventilation)

CaseHPOFreeText: on BiPAP, ambulatory (transport ventilator), juvenile-onset, assistive device (wheelchair)

CaseNotHPOs:

CaseNotHPOFreeText: no dysphagia at baseline, no tracheostomy

CasePreviousTesting: “GAA activity in peripheral blood leukocytes lower than normal”; on enzyme replacement therapy

PMID: 31392189

Gene: GAA

Disease: Pompe disease

Inheritance: Autosomal recessive

PMID: 31327549

Gene: GAA

Disease: Pompe Disease

Inheritance: Autosomal Recessive

Case#: Patient 1, gender N/A, Age of onset was 7-8 months (died at 3 years of age), Southeast Asian

DiseaseAssertion: Pompe Disease

FamilyInfo:

CasePresentingHPOs: HP:0001252, HP:0001270, HP:0001638, HP:0005165 (Muscular Hypotonia, Motor delay, Cardiomyopathy, Shortened PR interval)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: GAA activity in leukocytes was 0% of the normal control value.

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

Variant1: NM_000152.5(GAA):c.876C>G (p.Tyr292Ter)

ClinVar: 637958

CAID: CA401363871

gnomAD: N/A

Variant2: NM_000152.5:c.1003G>A (p.Gly335Arg)

ClinVar: 972790

CAID: CA501005

gnomAD: Highest population MAF = 0.00003266 (South Asian).

ParentalGenotype: Patient inherited variant 1 (NM_000152.5(GAA):c.876C>G (p.Tyr292Ter) from father.

Variant 2 (c.1003G>A (p.Gly335Arg)) was inherited from mother PreviouslyPublished:N/A

Case#: Patient 2, Gender N/A, 1-2 months old at onset, Southeast Asian

DiseaseAssertion: Pompe disease

FamilyInfo: Patient has two previously deceased siblings with cardiomyopathy

CasePresentingHPOs: HP:0002789, HP:0002240, HP:0005165, HP:0001639 (Tachypnea, Hepatomegaly, Shortened PR interval, Hypertrophic cardiomyopathy)

CaseHPOFreeText: BVH, EF 30%

CaseNotHPOs: N/A

CaseNotHPOFreeText:N/A

CasePreviousTesting: GAA activity in leukocytes was 0% of the normal control value

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

Variant1: NM_000152.5(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029

CAID: CA116610

gnomAD: Highes population MAF = 0.001729 (East Asian)

Variant2: NM_000152.5(GAA):c.1933G>C (p.Asp645His)

ClinVar:<br /> 189013

CAID: CA274256

gnomAD: Highest population MAF = 0.00005534 (East Asian)

ParentalGenotype: Father was carrier of variant 1 c.1935C>A ( p.Asp645Glu

Mother was carrier of the Variant 2 c.1933G>C (p.Asp645His

PreviouslyPublished:

PMID: 24399866

Gene: GAA

Case#: Case 2, Boy, Death at 7 months old, Hispanic

DiseaseAssertion: Pompe disease

FamilyInfo: Parents were carriers of the variant in Patient 2 (Figure 2.C)

CasePresentingHPOs: HP:0002205, HP:0001945, HP:0000980, HP:0001290, HP:0000158, HP:0002791, HP:0002240, HP:0200128

(Recurrent respiratory infections, Fever, Pallor, Generalized hypotonia, Macroglossia, Hypoventilation, Hepatomegaly, Biventricular hypertrophy )

CaseHPOFreeText: Systolic and diastolic dysfunction.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Ejection fraction was 40%

Serum Creatine Kinase levels were 650 IU/L

GAA enzyme activity on dried blood spots was 0.6 pmol/L, below normal levels (normal range: 10.0- 49 pmol/L).

Variant: c.1987delC

ClinVar: N/A

CAID: N/A

gnomAD: N/A

ParentalGenotype: Both parents are carriers of the variant c.1987delC

PreviouslyPublished: N/A

Case#: Case 1, Boy, Death at 6-7 months old, Hispanic

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002240, HP:0001640, 0000961, HP:0002090, HP:0001270, HP:0031664, HP:0200128, HP:0001252

(Hepatomegaly, Cardiomegaly, Cyanosis, Pneumonia, Motor delay, Systolic heart murmur, Biventricular hypertrophy, Muscular Hypotonia)

CaseHPOFreeText: Heart failure, Systolic murmur grade II-III, Enlarged, EKG showed an inverted T wave from V4-V6 as well as AVF, suggesting left systolic overload.

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: Ejection fraction of 52%

Serum creatine kinase was 386 IU/L (mildly elevated)

GAA activity on dried blood spot was decreased (1.08 nmol/L; normal range: 1.5-10 nmol/L)

Whole exon and exon-intron boundaries direct sequencing revealed a homozygous single base deletion c.1987delC

Variant: c.1987delC

ClinVar: N/A

CAID: N/A

gnomAD: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A