Case#: V.4, female, age of diagnosis 7 months, Moroccan

DiseaseAssertion: Pompe disease

FamilyInfo: Pedigree (figure 2). V.4 parents are cousins (IV.2 and IV.3). V.4 had a cousin (V.3) that died at 8 months of age and was diagnosed with HCM. V.3 parents (IV.1 and IV.4) are cousins. IV.2, IV.3, IV.1 and IV.4 were all heterozygous for the GAA mutation c.236_246del (p.Pro79ArgfsX13). V.4 was homozygous for the mutation.

CasePresentingHPOs: HP:0005157, HP:0001290

(Concentric hypertrophy, generalized hypotonia)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: hypotonia without facial dysmorphia or other associated abnormalities.

The heart was structurally normal and no valvular anomalies were observed.

CasePreviousTesting: whole exome sequencing (WES), Sanger sequencing. No metabolic screening was performed.

Molecular analysis of SMN gene excluded Spinal muscular atrophy, one of the major causes of neonatal hypotonia in Morocco.

Variant: NM_000152.5 c.236_246del (p.Pro79ArgfsX13)

ClinVar: 371302

CAID: CA16041880

gnomAD: N/A

ParentalGenotype: Both parents are heterozygous for .236_246del (p.Pro79ArgfsX13)

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 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 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#: Patient 3, Female, 2 months old at diagnosis, Caucasian

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001252, HP:0001638

(Muscular hypotonia, Cardiomyopathy)

CaseHPOFreeText: floppy baby, no head or neck control

NG tube feeds started at age 1.4 months, currently the patient orally feeds.

Before ERT patient needed oxygen, currently the patient does not need respiratory support.

CaseNotHPOs:

CaseNotHPOFreeText:

Patient ambulates independently

No infusion associated reactions to ERT

CasePreviousTesting: No GAA measurement

Variant: NM_000152.5(GAA):c.236_246del (p.Pro79fs)

ClinVar: 371302

CAID: CA16041880

gnomAD: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A