CaseII: Adult onset, 71 years diagnosis

CasePresentingHPOs: HP:0003701, HP:0003326, HP:0003236, HP:0003198 (Proximal muscle weakness, Myalgia, Increased serum CK, Myopathy)

HPOsFreeText: Plasma CK 5–10× Normal, GAA activity from dried blood spot: 0%, 6-Minute Walking Test: 40 min, Forced Vital Capacity Seated: 850 (22%)

CaseNotHPOs: HP:0002795 (Abnormal respiration)

CaseAddInfo: Late-Onset Pompe Disease

GroupPresentingHPOs: HP:0003325, HP:0003457, HP:0012548, HP:0004887, HP:0010535, HP:0001712, HP:0031296

HPOsFreeText: hyperCKaemia+LGMW, BMI, mean (SD) 25.2±5.8, Serum CK, mean (SD) 600±302, vacuolar myopathy, Muscle GAA %, mean (SD) 9.4±3.8, myogenic EMG, abnormal MRI, %Predicted FVC, mean (SD) 73±11, 6MWT, mean (SD) 452±9, vacuolisation of myofibers with variable glycogen storage, AP staining low in 6 individuals, medium in five, and high in 2 individuals. Low residual GAA activity in muscles,

GroupNotHPOs:

NotHPOsFreeText:

NumberMales: 8

NumberFemales: 9

CountryOrigin: n/a

AgeRange: mean (SD) 40±14.36

TotalNumber: 14

GroupAddInfo: mean age at disease onset was 40±14.3 years, median age at disease diagnosis was 47±14 years. 14 of the individuals underwent enzyme replacement therapy. Blood CK levels increased in all but one individual.

GroupGenotypingMethod: GAA gene sequencing

Variant 1: NM_000152.4(GAA):c.-32-13T>G

ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

Variant 2: p.P522A, NM_000152.4(GAA):c.1564C>G (p.Pro522Ala)

ClinVar: 371277, https://www.ncbi.nlm.nih.gov/clinvar/variation/371277/

gnomAD: n/a

Case# Patient 4, female

CasePresentingHPOs: HP:0003236, HP:0003325

CaseAddInfo: 31yo at onset, 40yo at diagnosis

VariantAllele1: NM_000152.4(GAA):c.-32-13T>G

ClinVar: 4027, https://www.ncbi.nlm.nih.gov/clinvar/variation/4027/

gnomAD: 0.003582, http://exac.broadinstitute.org/variant/17-78078341-T-G

VariantAllele2: NM_000152.4(GAA):c.1564C>G (p.Pro522Ala)

ClinVar: 371277, https://www.ncbi.nlm.nih.gov/clinvar/variation/371277/

gnomAD: n/a

Case#: LOPD patient #1, Male, 69, ethnicity unknown.

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002094, HP:0006554, HP:0012378, HP:0001324 (Dyspnea, Acute respiratory failure, Fatigue, Lower Girdle Muscle Weakness and Upper Girdle Muscle Weakness)

CaseHPOFreeText: Dyspnea was present during exercise, not at rest. Lower Girdle Muscle Weakness and Upper Girdle Muscle Weakness share the same HPO.

CaseNotHPOs:

CaseNotHPOFreeText: Patient has normal creatine phosphokinase levels, No Dyspnea at rest, No Ortopnea, No Airways infections, no myalgia

CasePreviousTesting: GAA gene sequencing to asses genotype.

GAA activity was reduced (0.36 microMol/L/h) in reference to standard (10.1 ± 6.6 microMol/L/h) This was measured by dried blood spot .

GAA muscle activity was 3.6 pmol/min/mg, no reference range was provided

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

ClinVar: 4027

CAID: CA116606

gnomAD: MAF= 0.005541 (Ashkenazi Jewish)

Variant 2: NM_000152.5(GAA):c.1564C>G (p.Pro522Ala)

ClinVar:371277

CAID:CA16041893

gnomAD: N/A

ParentalGenotype: N/A

PreviouslyPublished: N/A

Patient20: Female

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

HPOsFreeText: CRIM positive, Anti-rh GGA antibodies maximum titer = 1:1.600, tracheostomy, partial heart normalization, moderate periventricular white matter abnormalities (hypomyelination)

CaseNotHPOs: HP:0002421, HP:0001371

NotHPOsFreeText: infusion associated reaction

CaseAddInfo: homozygous variant in trans, symtom onset and diagnosis at 4yo, ERT at 5yo

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.1564C>G (p.Pro522Ala)

ClinVar: 371277, https://www.ncbi.nlm.nih.gov/clinvar/variation/371277/

gnomAD: n/a