10
Case10: Female, 15 years report, Italy
HPOsFreeText: Height is 1.60 m, Weight is 59 kg, BMI is 23.0 kg/cm2, 8 years on ERT, Forced Vital Capacity at 106%
CaseNotHPOs: HP:0002098 (Respiratory distress)
NotHPOsFreeText: Nocturnal non-invasive ventilation
CaseAddInfo: Late Onset Pompe Disease
4
Case4: 0.5 years diagnosis, Germany
CasePresentingHPOs: HP:0031185, HP:0001635, HP:0001252, HP:0001324, HP:0003236, HP:0001639 (Increased NT-proBNP level, Cardiac failure, Muscular hypotonia, Muscle weakness, Increased serum CK, Hypertrophic cardiomyopathy)
HPOsFreeText: 3924 BNP (pg/ml), 7.68 IVS (d) z score, 6.42 IVS (s) z score, Heart Failure at NYHA Class 3
NotHPOsFreeText: No left-ventricular outflow tract obstruction
CaseAddInfo: Infantile-Onset Pompe Disease
4a
Case4a: Male, 46 years onset, 46 years diagnosis, 56 years report
CasePresentingHPOs: HP:0003236, HP:0002747 (Increased serum CK, Respiratory muscle weakness)
CaseAddInfo: Late-Onset Pompe Disease, Sibling of Patient 4
4
Case4: Female, 25 years onset, 43 years diagnosis, 58 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, Sibling of Patient 4a
20
Case20: Male, 14 yr diagnosis, 15.2 yr report
HPOsFreeText: FVC z-score sitting 3 (135% pred), FVC z-score supine 1.72 (120% pred), 1409 CK U/l, Deficent GAA activity (nmol/h/mg)^h from cultured fibroblasts
NotHPOsFreeText: No wheelchair used, No respiratory support
16
Case16: Male, 12 yr onset, 8 yr diagnosis, 14.6 yr report
HPOsFreeText: FVC z-score sitting -2.43 (71% pred), 82% MRC Scale, 1808 CK U/l, Deficent GAA activity (nmol/h/mg)^h from cultured fibroblasts
NotHPOsFreeText: No wheelchair used, No respiratory support
21
Case21: Male, 16 yr diagnosis, 17.1 yr report
HPOsFreeText: FVC z-score sitting 1.29 (115% pred), FVC z-score supine -0.25 (97% pred), 1506 CK U/l, Deficent GAA activity (nmol/h/mg)^h from cultured fibroblasts
NotHPOsFreeText: No wheelchair used, No respiratory support
Detailed characteristics of these patients
Patient2: female, 16yo, juvenile onset
CasePresentingHPOs:
HPOsFreeText: LOPD, BMI = 17.7;20.3;20.3, WGMS = 2;2;2
CaseNotHPOs: HP:0002355
NotHPOsFreeText: did not require respiratory support
CaseAddInfo:
CasePMIDs:
CasePreviousTesting: same as group
CaseGenotypingMethod: same as group
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.307T>G (p.Cys103Gly)
ClinVar: 92483, https://www.ncbi.nlm.nih.gov/clinvar/variation/92483/
gnomAD: n/a
IOPD-4
CaseIOPD-4: 3 min diagnosis
CasePresentingHPOs: HP:0003236, HP:0001638 (Increased serum CK, Cardiomyopathy)
HPOsFreeText: GAA activity 0.6 (nmol · h−1 · mg−1), Mean percentage of normal 0.9%
GenotypingMethod: Newborn Screening Panels
Variant1: NM_000152.4:c.271G>A (p.Asp91Asn)
ClinVar: 4020 https://www.ncbi.nlm.nih.gov/clinvar/variation/4020/
gnomAD: European (Non-Finnish) 0.03291, Overall 0.02049 http://gnomad.broadinstitute.org/variant/17-78078656-G-A
Variant2: NM_000152.4:c.307T>G (p.Cys103Gly)
ClinVar: 92483 https://www.ncbi.nlm.nih.gov/clinvar/variation/92483/
gnomAD: European (non-Finnish) 7.874e-6, Overall 3.578e-6 http://gnomad.broadinstitute.org/variant/17-78078692-T-G
Variant3: NM_000152.4:c.1000G>T (p.Gly334Cys)
ClinVar: 284864 https://www.ncbi.nlm.nih.gov/clinvar/variation/284864/
gnomAD: Not in gnomAD
CaseAddInfo: Infantile Onset Pompe Disease, Nomenclature claims Variant 1 and 2 are in cis
P16a
Patient16: Female, 49yo
CasePresentingHPOs: HP:0003077
HPOsFreeText: LOPD
CaseNotHPOs:
NotHPOsFreeText:
CaseAddInfo: 23yr disease duration, ERT lasted 119mo, 5yr follow-up MRI
CasePMIDs:
CasePreviousTesting: same as group
CaseGenotypingMethod: same as group
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.307T>G (p.Cys103Gly)
ClinVar: 92483, https://www.ncbi.nlm.nih.gov/clinvar/variation/92483/
gnomAD: n/a
P7a
Patient7: Male, 59yo
CasePresentingHPOs: HP:0000822, HP:0000819, HP:0003077, HP:0001513
HPOsFreeText: LOPD
CaseNotHPOs:
NotHPOsFreeText:
CaseAddInfo: 5yr follow-up MRI, 14yr disease duration, ERT lasted for 135mo
CasePMIDs: PMID: 25614309
CasePreviousTesting: same as group
CaseGenotypingMethod: same as group
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.307T>G (p.Cys103Gly)
ClinVar: 92483, https://www.ncbi.nlm.nih.gov/clinvar/variation/92483/
gnomAD: n/a
2
Case#: Patient 2, female, diagnosed 2010 (not given age), age 43 during study period
DiseaseAssertion: Pompe Disease
FamilyInfo: None given
CasePresentingHPOs: None given
CaseHPOFreeText: None given
CaseNotHPOs: None given
CaseNotHPOFreeText: None given
CasePreviousTesting: None given
Variant 1: NM_000152.5:c.-32-13T>A
Variant 1 ClinVarID:
Variant 1 CAid: CA913184742
Variant 2: NM_000152.5:c.307T>G
Variant 2 ClinVarID: 92483
Variant 2 CAid: CA220404
ParentalGenotype: Not provided
1
Case1: Female, Danish, 38 years report, 25 years onset
CasePresentingHPOs: HP:0008956 (Thigh muscle atrophy)
HPOsFreeText: 6-min walk test achieved 531 m, MRC score is 4/5 (thigh/calf), Forced vital capacity sitting/supine is 2.8/2.2 (L)
NotHPOsFreetext: Not on ERT
GroupGenotypingMethod: Mutation Analysis on the GAA Gene
Variant1: NM_000152.4:c.-32-13T>A
CAID: CA913184742 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA913184742
gnomAD: Not in gnomAD
Variant2: NM_000152.4:c.307T>G (p.Cys103Gly)
ClinVar: 92483 https://www.ncbi.nlm.nih.gov/clinvar/variation/92483/
gnomAD: European (Non-Finnish) 7.874e-6, Overall 3.578e-6 http://gnomad.broadinstitute.org/variant/17-78078692-T-G
CaseAddInfo: Late Onset Pompe Disease
Ten patients received concomitant immunomodulation (detailed in Supplementary Table S4); six were genotype-predicted as CRIM-negative, three were CRIM-positive, and one lacked genotype data.
Patient 3
Variant1: NM_000152.3:c.2481+102_2646+31del
CAID: CA658795291, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.3%3Ac.2481%2B102_2646%2B31del
gnomAD: n/a
Variant2: NM_000152.4(GAA):c.307T>G (p.Cys103Gly)
ClinVar: 92483, https://www.ncbi.nlm.nih.gov/clinvar/variation/92483/
gnomAD: n/a
16
Case#: Subject number 16, male, 64 years (report), 56 years (onset), 60 years (diagnosis)
DiseaseAssertion: Pompe disease
FamilyInfo: N/A
CasePresentingHPOs:
CaseHPOFreeText: on BiPAP, ambulatory, assistive device (cane)
CaseNotHPOs: HP:0009830, HP:0000360, HP:0002650, HP:0000939, HP:0000821, HP:0000365, HP:0002617, HP:0100647, HP:0010788, HP:0001638 (peripheral neuropathy, tinnitus, scoliosis, osteoporosis, hypothyroidism, hearing loss, aneurysm, Graves disease, Testicular cancer, cardiomyopathy)
CaseNotHPOFreeText: no infusion reaction, no tracheostomy
CasePreviousTesting: “documented deficiency of acid alpha-glucosidase enzyme activity”; on enzyme replacement therapy
Variant 1: NM_000152.5(GAA):c.-32-13T>G (p.Tyr766Ser)
Variant 1 ClinVarID: 4027
Variant 1 CAid: CA116606
Variant 2: NM_000152.5(GAA):c.307T>G
Variant 2 ClinVarID: 92483
Variant 2 CAid: CA220404
Zygosity: Compound heterozygous
ParentalGenotype: N/A