Patient1: 7yo

CasePresentingHPOs: HP:0001638

HPOsFreeText: rhGAA dosage = 20QW, independent walker

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 17days old at ERT start

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: 0.0001721, http://exac.broadinstitute.org/variant/17-78086721-C-A

Variant2: NM_000152.4(GAA):c.784G>A (p.Glu262Lys)

ClinVar: 188806, https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

gnomAD: 1.66e-05, http://exac.broadinstitute.org/variant/17-78081447-G-A

Patient25: Female

CasePresentingHPOs: HP:0004887

HPOsFreeText: CRIM positive, Anti-rh GGA antibodies maximum titer = ≤ 1:400, tracheostomy, able to sit independently

CaseNotHPOs: HP:0025156, HP:0002546, HP:0000365

NotHPOsFreeText: infusion associated reaction

CaseAddInfo: variants in trans, symptom onset at 2yo, diagnosis at 3yo, ERT at 4yo

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.784G>A (p.Glu262Lys)

ClinVar: 188806, https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

gnomAD: 0.00001417, http://gnomad.broadinstitute.org/variant/17-78081447-G-A

Patient18: Male

CasePresentingHPOs: HP:0004887, HP:0001270, HP:0002546

HPOsFreeText: CRIM positive, Anti-rh GGA antibodies maximum titer = ≤ 1:400, heart normalization

CaseNotHPOs: HP:0025156, HP:0000365, HP:0001371

NotHPOsFreeText: infusion associated reaction

CaseAddInfo: homozygous variants in trans, symptom onset at 1yo, diagnosis at 1.5yo, ERT at 4yo

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.784G>A (p.Glu262Lys)

ClinVar: 188806, https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

gnomAD: 1.66e-05, http://exac.broadinstitute.org/variant/17-78081447-G-A

Case#: Patient 3, female

CasePresentingHPOs: HP:0003236

CaseAddInfo: 29yo at onset, 39yo 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.784G>A (p.Glu262Lys)

ClinVar: 188806, https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

gnomAD: 1.66e-05, http://exac.broadinstitute.org/variant/17-78081447-G-A

CaseVII: Adolescent onset, 33 years diagnosis

CasePresentingHPOs: HP:0003701, HP:0003236, HP:0002460, HP:0003394 (Proximal muscle weakness, Increased serum CK, Distal muscle weakness, Muscle cramps)

HPOsFreeText: GAA activity from dried blood spot: 0.20%, Forced Vital Capacity Seated: 5260 (112%), Plasma CK 2.5-5x Normal, Vacuoles in histology

CaseNotHPOs: HP:0002795 (Abnormal respiration)

CaseAddInfo: Late-Onset Pompe Disease

Case13: 56yo

CasePresentingHPOs: HP:0003325, HP:0002093, HP:0004887, HP:0020038

HPOsFreeText: GAA = 6.3%, BMI = 22.5, nucleo-capsular and subcortical white matter lacunes

CaseNotHPOs:

NotHPOsFreeText: No cardiovascular risk

CaseAddInfo: 24yr disease duration, variants in trans

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: 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

Variant2: NM_000152.4(GAA):c.784G>A (p.Glu262Lys)

ClinVar: 188806, https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

gnomAD: 1.66e-05, http://exac.broadinstitute.org/variant/17-78081447-G-A

Case85

HPOsFreeText: See Group Phenotypes

CasePreviousTesting: Sanger sequencing

CaseMethod1: Sanger sequencing and PCR Amplification

CaseMethod2: Whole Exome Sequencing (WES)

CaseGenotypingMethod: Patients were previously confirmed with Pompe disease by Sanger sequencing to capture the pathogenic variants. The process was repeated as part of the study taking care to amplify the coding regions and exon/intron boundaries to compare with the WES results afterwards.

Variant1: NM_000152.4:c.784G>A (p.Glu262Lys)

ClinVar: 188806 https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

gnomAD: East Asian 5.016e-5, Overall 1.417e-5 http://gnomad.broadinstitute.org/variant/17-78081447-G-A

Variant2: NM_000152.4:c.-32-13T>G

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

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

CaseAddInfo: Adult Late Onset Pompe Disease, 2 other patients have the same genotype

CaseOPOPD-38: Female, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 0.56 umol/hr/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.784G>A (p.Glu262Lys)

ClinVar: 188806 https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

gnomAD: East Asian 5.016e-5, Overall 1.417e-5 http://gnomad.broadinstitute.org/variant/17-78081447-G-A

Variant2: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

CaseAddInfo: One Pompe Mutation allele and One Pseudodeficency Mutation allele

Patient5: Female

CasePresentingHPOs: HP:0004887, HP:0002194, HP:0001522

HPOsFreeText: ERT dosage = 20 mg/kg/2 w, CRIM positive

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: Symptom onset at 2mo, diagnosis and ERT at 4mo, ERT lasted for 1mo, ventilation required at 3mo, died at 5mo, variants in trans

CasePMIDs: 21763167, 11738358

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.784G>A (p.Glu262Lys)

ClinVar: 188806, https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

gnomAD: 1.66e-05, http://exac.broadinstitute.org/variant/17-78081447-G-A

Variant2: NM_000152.4(GAA):c.1802C>T (p.Ser601Leu)

ClinVar: 194154, https://www.ncbi.nlm.nih.gov/clinvar/variation/194154/

gnomAD: 0.00003187, http://gnomad.broadinstitute.org/variant/17-78086424-C-T

CaseI: Early adult onset, 49 years diagnosis

CasePresentingHPOs: HP:0003701, HP:0003388, HP:0003236, HP:0003198 (Proximal muscle weakness, Easy fatigability, Increased serum CK, Myopathy)

HPOsFreeText: Plasma CK 5–10× Normal, GAA activity from lymphocytes: 14.2%

CaseNotHPOs: HP:0002795 (Abnormal respiration)

CaseAddInfo: Late-Onset Pompe Disease

Case10: Male, 50 years onset, 52 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 53, GAA Activity at ~13 pmol/min/mg before ERT and ~15 after

GroupGenotypingMethod: PCR Amplification and GAA Gene Sequencing

Variant1: NM_000152.4:c.-32-13T>G

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

gnomAD: Ashkenazi Jewish 5.541e-3, Overall 3.401e-3 http://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.784G>A (p.Glu262Lys)

ClinVar: 188806 https://www.ncbi.nlm.nih.gov/clinvar/variation/188806/

gnomAD: East Asian 5.016e-5, Overall 1.417e-5 http://gnomad.broadinstitute.org/variant/17-78081447-G-A

CaseAddInfo: Late Onset Pompe Disease