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#: case 1, male, 3 months old at diagnosis, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001638, HP:0001252 (cardiomyopathy, muscular hypotonia)

CaseHPOFreeText: (Associated with Pompe Disease): Interventricular septum hypertrophy, increased serum CK, increased serum tryptase

CaseHPOFreeText: (Infussion associated reactions) Urticarial rash, unresponsive to antihistamines and corticosteroids

CaseNotHPOs:

CaseNotHPOFreeText: Infusion associated reactions are not associated with an IgE mediated mechanism.

CasePreviousTesting:

GAA activity on fibroblast is 0.8 nmol/mg prot/h with a reference range of 64.4 ± 22.9 nmol/mg prot/h

GAA activity on lymphocytes is 2.2 nmol 4 Mu/mg prot/h with a reference range of 21.4 ± 6.2 nmol 4 Mu/mg prot/h

Variants:<br /> Variant 1: NM_000152.5(GAA):c.236_246del (p.Pro79fs)

ClinVar: 371302

CAID: 16041880

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

ClinVar:279811

CAID: 8815429

gnomAD: N/A

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 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