Case#: Patient 1, woman, 58 years old, ethnicity unknown

DiseaseAssertion:Pompe disease

Was also misdiagnosed with adult-onset spinal muscular atrophy (SMA)

FamilyInfo: No family history of muscle disease

CasePresentingHPOs: HP:0003701, HP:0100284

(Proximal muscle weakness, EMG myotonic discharges)

CaseHPOFreeText: Denervation atrophy from a muscle biopsy

Weakness of hip flexion 2–3/5, hip abduction 2/5, and hip adduction 2/5

Myotonic discharges were in the lumbar paraspinals, vastus medialis, and tensor fasciae latae muscles.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: GAA enzyme activity assay was 1 pmol/punch/h (normal range 10–49 pmol/punch/h)

Her creatine kinase (CK) level at presentation had been elevated as high as 429 U/L (normal range 45–145)

Found with two mutations in the GAA gene

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

ClinVar: 4027

CAID: CA116606

gnomAD: Highest population MAF= 0.005541 (Ashkenazi Jewish)

Variant: NM_000152.5(GAA):c.525del (p.Glu176fs) Double check this variant

ClinVar: 4033

CAID: CA220406

gnomAD: N/A

ParentalGenotype:N/A

Previously Published: 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

Case#: Patient 6, gender unknown, age unknown, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001638, HP:0003756

(Cardiomyopathy, Skeletal myopathy)

CaseHPOFreeText:N/A

CaseNotHPOs: N.A

CaseNotHPOFreeText: N/A

CasePreviousTesting: Sequence analysis of the GAA gene was performed in a CLIA and CAP certified laboratory.

Cross Reactive Immune reaction was negative in peripheral blood mononuclear cells (PBMCs)

Cross Reactive Immune reaction was not available in Dried blood spots.

Variant: NM_000152.5(GAA):c.2297A>C (p.Tyr766Ser)

ClinVar: 420102

CAID: CA8815680

gnomAD: Highest population MAF= 0.00005441 (East asian)

ParentalGenotype: N/A

PreviouslyPublished:N/A