CaseIX: Early adult onset

CasePresentingHPOs: HP:0003701, HP:0003388, HP:0002795, HP:0001627 (Proximal muscle weakness, Easy fatiguability, Abnormal respiration, Abnormal heart morphology)

HPOsFreeText: Wheelchair-bound

CaseAddInfo: Late-Onset Pompe Disease

CaseV,1: Adolescent onset, 42 years diagnosis

CasePresentingHPOs: HP:0003701, HP:0003236, HP:0003388, HP:0003326 (Proximal muscle weakness, Increased serum CK, Easy fatigability, Myalgia)

HPOsFreeText: Plasma CK 5-10× Normal, Vacuoles in histology, 6-Minute Walking Test: 135 min, Forced Vital Capacity Seated: 950 (20%), GAA activity from dried blood spot: 0.20%

CaseNotHPOs: HP:0002795 (Abnormal respiration)

CaseAddInfo: Late-Onset Pompe Disease

CaseIV,1: Early adult onset, 40 years diagnosis

CasePresentingHPOs: HP:0003701, HP:0003236, HP:0002795, HP:0003546 (Proximal muscle weakness, Increased serum CK, Abnormal respiration, Exercise intolerance)

HPOsFreeText: Plasma CK 2.5–5× Normal, Vacuoles in histology

CaseAddInfo: Late-Onset Pompe Disease

CaseV,3: Child onset, 45 years diagnosis

CasePresentingHPOs: HP:0003701, HP:0003236 (Proximal muscle weakness, Increased serum CK)

HPOsFreeText: Plasma CK 2.5-5× Normal, GAA activity from dried blood spot: 0.08%, 6-Minute Walking Test: 566 min

CaseNotHPOs: HP:0002795 (Abnormal respiration)

CaseAddInfo: Late-Onset Pompe Disease

CaseIV,4: Early adult onset, 45 years diagnosis

CasePresentingHPOs: HP:0003701, HP:0003236, HP:0003546 (Proximal muscle weakness, Increased serum CK, Exercise intolerance)

HPOsFreeText: Plasma CK 2.5–5× Normal, Vacuoles in histology

CaseNotHPOs: HP:0002795 (Abnormal respiration)

CaseAddInfo: Late-Onset Pompe Disease

CaseIV,3: Early adult onset, 50 years diagnosis

CasePresentingHPOs: HP:0003236, HP:0003546 (Increased serum CK, Exercise intolerance)

HPOsFreeText: Plasma CK 2.5–5× Normal

CaseNotHPOs: HP:0002795 (Abnormal respiration)

CaseAddInfo: Late-Onset Pompe Disease

CaseV,2: Adult onset, 33 years diagnosis

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

HPOsFreeText: Plasma CK 5-10× Normal, 6-Minute Walking Test: 566 min, Forced Vital Capacity Seated: 3000 (90%), GAA activity from dried blood spot: 0.20%

CaseNotHPOs: HP:0002795 (Abnormal respiration)

CaseAddInfo: Late-Onset Pompe Disease

CaseIV,2: Early adult onset, 47 years diagnosis

CasePresentingHPOs: HP:0003701, HP:0003236, HP:0002795, HP:0003546 (Proximal muscle weakness, Increased serum CK, Abnormal respiration, Exercise intolerance)

HPOsFreeText: Plasma CK 2.5–5× Normal

CaseAddInfo: Late-Onset Pompe Disease

Patient3: female

CasePresentingHPOs: HP:0001270, HP:0001371

HPOsFreeText: CRIM positive, partial heart normalization

CaseNotHPOs: HP:0004887, HP:0025156

NotHPOsFreeText: infusion associate reaction

CaseAddInfo: symptom onset at 1yo, diagnosis and ERT at 5yo. Died due to failure to respond to ERT.

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant 1-3 in cis

Variant1: NM_000152.3:c.1833_1839del

CAID: CA913184757, http://reg.clinicalgenome.org/redmine/projects/registry/gene_indel

gnomAD: n/a

Variant2: NM_000152.3:c.1846G>T

CAID: CA401369607, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA401369607

gnomAD: n/a

Variant3: NM_000152.3:c.1847_1848insT

CAID: CA913184758, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA913184758

gnomAD: n/a

Variant4: NM_000152.4(GAA):c.1124G>T (p.Arg375Leu)

ClinVar: 283230, https://www.ncbi.nlm.nih.gov/clinvar/variation/283230/

gnomAD: 8.561e-06, http://exac.broadinstitute.org/variant/17-78082336-G-T

Patient7:

CasePresentingHPOs:

HPOsFreeText: classic IOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: homozygous

CasePMIDs:

CasePreviousTesting:

CaseGenotypingMethod: method not described

Variant: NM_000152.4(GAA):c.1124G>T (p.Arg375Leu)

ClinVar: 283230, https://www.ncbi.nlm.nih.gov/clinvar/variation/283230/

gnomAD: 0.000008050, https://gnomad.broadinstitute.org/variant/17-78082336-G-T