PatientF3P1: Female, 3 months diagnosis, Multiracial (maternal European and Native American and paternal Czechoslovakian, German, and Australian)

CasePresentingHPOs: HP:0004755, HP:0001290 (Supraventricular tachycardia, Generalized hypotonia)

CaseAddInfo: Proband

PatientF3P2: Female, 36 years diagnosis, European and Native American

CasePresentingHPOs: HP:0003236, HP:0012378, HP:0003547, HP:0009113, HP:0002910 (Increased serum CK, Fatigue, Shoulder weakness, Weak diaphragm, Increased transaminases)

HPOsFreeText: Decline in energy and strength reported with each of her four pregnancies most prominent after her youngest daughter's diagnosis of IOPD, Subsequent enzyme assay indicated deficient GAA activity via a dried blood spot (2.2 pmol/punch/hr, control >3.88 pmol/punch/hr), Pulmonary functioning tests (PFTs) showed a decrease in forced vital capacity (FVC) from 93% predicted seated to 72% predicted supine, Laboratory results demonstrated an elevated CK level of 490 U/L (control 30–220 U/L) and mild elevation of transaminases with AST of 83 U/L (control 15–41 U/L) and ALT of 60 U/L (control 14–54 U/L)

CaseAddInfo: Mother of proband F3P1, found to have minimally symptomatic LOPD

Case38

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.2481+102_2646+31del (p.Gly828_Asn882del) (exon 18 del)

ClinVar: 4031 https://www.ncbi.nlm.nih.gov/clinvar/variation/4031/

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.1912G>T (p.Gly638Trp)

CAID: 280954 https://www.ncbi.nlm.nih.gov/clinvar/variation/280954/

gnomAD: African 6.752e-5, Overall 1.239e-5 http://gnomad.broadinstitute.org/variant/17-78086698-G-T

CaseAddInfo: Infantile Onset Pompe Disease

Case2: Female, 44 years onset, 54 years diagnosis, 65 years report

CasePresentingHPOs: HP:0003325, HP:0003327, HP:0003236, HP:0002747 (Limb-girdle muscle weakness, Axial muscle weakness, Increased serum CK, Respiratory muscle weakness)

CaseAddInfo: Late-Onset Pompe Disease