Subject II-6: female, 56yo

CasePresentingHPOs: HP:0000822, HP:0003701, HP:0001611, HP:0003691, HP:0003700, HP:0009023, HP:0003307, HP:0002515, HP:0040081, HP:0003458

HPOsFreeText: altered DBS, treated with beta-blockers, occasional cramping of lower limbs, muscle atrophy of temporal, deltoids, and thigh muscle extensors, muscle strength was 5/5 proximal and distal for upper limbs and distal for lower limbs, and 4/5 on hip extension, diminished biceps, triceps, patellar, and ankle jerk reflexes. Intact pain, temperature, vibration, proprioception, and coordination. CK = 86 IU/L, AST = 33 IU/L, reduced GAA activity, reduced duration and amplitude of motor unit action potentials (mainly on thigh extensors), normal muscle biopsy

CaseNotHPOs: HP:0001291, HP:0002015, HP:0001618, HP:0003391, HP:0003487

NotHPOsFreeText: no Hoffmann sign, paraspinal complex repetitive discharges

CaseAddInfo: This patient's 5 daughters had DBS and GAA sequencing evaluations, only 2 (III-9 and III-10) had altered DBS and carried GAA variants

CasePMIDs:

CasePreviousTesting: DBS, EMG, muscle biopsy from thigh extensors

CaseGenotypingMethod: GAA genotyping

Variant1: 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.2560C>T (p.Arg854Ter)

ClinVar: 4034, https://www.ncbi.nlm.nih.gov/clinvar/variation/4034/

gnomAD: 0.0002090, http://gnomad.broadinstitute.org/variant/17-78092070-C-T

Subject II-4: female

CasePresentingHPOs:

HPOsFreeText: normal GAA enzyme values

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: carrier status, clinically asymptomatic

CasePMIDs:

CasePreviousTesting: DBS

CaseGenotypingMethod: GAA genotyping

Variant: NM_000152.4(GAA):c.2560C>T (p.Arg854Ter)

ClinVar: 4034, https://www.ncbi.nlm.nih.gov/clinvar/variation/4034/

gnomAD: 0.0002090, http://gnomad.broadinstitute.org/variant/17-78092070-C-T

Case77

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.2560C>T (p.Arg854*)

ClinVar: 4034 https://www.ncbi.nlm.nih.gov/clinvar/variation/4034/

gnomAD: African 1.891e-3, Overall 2.090e-4 http://gnomad.broadinstitute.org/variant/17-78092070-C-T

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

Case21

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.2560C>T (p.Arg854*)

ClinVar: 4034 https://www.ncbi.nlm.nih.gov/clinvar/variation/4034/

gnomAD: African 1.891e-3, Overall 2.090e-4 http://gnomad.broadinstitute.org/variant/17-78092070-C-T

Variant2: NM_000152.4:c.1129G>C (p.Gly377Arg)

ClinVar: 497033 https://www.ncbi.nlm.nih.gov/clinvar/variation/497033/

gnomAD: European (Non-Finnish) 2.356e-5, Overall 1.072e-5 http://gnomad.broadinstitute.org/variant/17-78082341-G-C

CaseAddInfo: Infantile Onset Pompe Disease