Patient1: Female, northern China

CasePresentingHPOs:

HPOsFreeText: IOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.2662G>T (p.Glu888Ter)

ClinVar: 578595, https://www.ncbi.nlm.nih.gov/clinvar/variation/578595/

gnomAD: 1.65e-05, http://exac.broadinstitute.org/variant/17-78092467-G-T

Variant2: NM_000152.4(GAA):c.1927G>A (p.Gly643Arg)

ClinVar: 4023, https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

Patient1: Female, northern China

CasePresentingHPOs:

HPOsFreeText: IOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.2662G>T (p.Glu888Ter)

ClinVar: 578595, https://www.ncbi.nlm.nih.gov/clinvar/variation/578595/

gnomAD: 1.65e-05, http://exac.broadinstitute.org/variant/17-78092467-G-T

Variant2: NM_000152.4(GAA):c.1927G>A (p.Gly643Arg)

ClinVar: 4023, https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: 0.00002479, http://gnomad.broadinstitute.org/variant/17-78086713-G-A

Patient13: female

CasePresentingHPOs: HP:0004887, HP:0011471, HP:0001270, HP:0002546, HP:0000365

HPOsFreeText: CRIM positive, tracheostomy, partial heart normalization

CaseNotHPOs: HP:0001371

NotHPOsFreeText: infusion associated reaction

CaseAddInfo: variants in trans, symptom onset at 6yo, diagnosis and ERT at 11yo

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.236_246delCCACACAGTGC (p.Pro79Argfs)

ClinVar: 371302, https://www.ncbi.nlm.nih.gov/clinvar/variation/371302/

gnomAD: n/a

Variant2: NM_000152.4(GAA):c.1927G>A (p.Gly643Arg)

ClinVar: 4023, https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: 5.884e-05, http://exac.broadinstitute.org/variant/17-78086713-G-A

CaseIII: Adult onset, 63 years diagnosis

CasePresentingHPOs: HP:0003701, HP:0003388, HP:0003236, HP:0003198, HP:0002460, HP:0002015 (Proximal muscle weakness, Easy fatigability, Increased serum CK, Myopathy, Distal muscle weakness, Dysphagia)

HPOsFreeText: Plasma CK 2.5–5× Normal, GAA activity from muscle: 11.7%

CaseNotHPOs: HP:0002795 (Abnormal respiration)

CaseAddInfo: Late-Onset Pompe Disease

Case1: Male, 51 years report, 50 years diagnosis, Germany

CasePresentingHPOs: HP:0002878 (Respiratory failure)

HPOsFreeText: 6-min walk test at 484 (m)

CaseNotHPOs: register NotHPOsFreeText: Not wheelchair bound

CaseAddInfo: 1.5 years on ERT

Patient2: female

CasePresentingHPOs: HP:0004887, HP:0002194, HP:0001263, HP:0002463, HP:0002870, HP:0011003, HP:0002289

HPOsFreeText: ERT dosage = 20 mg/kg/2 w, use of BiPAP, could sit independently, HCM reversal, CRIM positive, BiPAP ventilation at night

CaseNotHPOs: HP:0000407

NotHPOsFreeText:

CaseAddInfo: Symptom onset and diagnosis at 1d, ERT at 3w, required BiPAP at 57mo, ERT lasted for 77mo, currently 6.5yo

CasePMIDs: 8401535

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.1927G>A (p.Gly643Arg)

ClinVar: 4023, https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: 5.884e-05, http://exac.broadinstitute.org/variant/17-78086713-G-A

Patient22: Female

CasePresentingHPOs: HP:0004887, HP:0011471, HP:0001371

HPOsFreeText: CRIM positive, tracheostomy, able to sit independently, heart normalization

CaseNotHPOs: HP:0002546, HP:0000365

NotHPOsFreeText: infusion associated reaction

CaseAddInfo: homozygous variants in trans, symptom onset and diagnosis at 4yo, ERT at 5yo

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.1927G>A (p.Gly643Arg)

ClinVar: 4023, https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: 0.00002479, http://gnomad.broadinstitute.org/variant/17-78086713-G-A

Patient 21: Female

CasePresentingHPOs: HP:0004887, HP:0011471, HP:0002546, HP:0000365, HP:0001371, HP:0100845

HPOsFreeText: CRIM positive, infusion associated reaction, tracheostomy, able to sit independently, heart normalization

CaseNotHPOs:

CaseAddInfo: variants in trans, symptom onset at birth, diagnosis at 19 days, ERT at 1yo

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.3:c.930_932del

CAID: CA913184760, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA913184760

Variant2: NM_000152.4(GAA):c.1927G>A (p.Gly643Arg)

ClinVar: 4023, https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: 0.00002479, http://gnomad.broadinstitute.org/variant/17-78086713-G-A

Case3: Male, 30 years onset, 66 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 67, GAA Activity at ~8 pmol/min/mg before ERT and ~10 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.1927G>A (p.Gly643Arg)

ClinVar: 4023 https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: European (Non-Finnish) 3.667e-5, Overall 2.479e-5 http://gnomad.broadinstitute.org/variant/17-78086713-G-A

CaseAddInfo: Late Onset Pompe Disease

Case1: Male, 21 years onset, 31 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 31, GAA Activity at ~7.5 pmol/min/mg before ERT and ~8 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.1927G>A (p.Gly643Arg)

ClinVar: 4023 https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: European (Non-Finnish) 3.667e-5, Overall 2.479e-5 http://gnomad.broadinstitute.org/variant/17-78086713-G-A

CaseAddInfo: Late Onset Pompe Disease

Case4: Female, 40 years onset, 51 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 51, GAA Activity at ~7.5 pmol/min/mg before ERT and ~11 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.525delT (p.Glu176Argfs*45)

ClinVar: 4033 https://www.ncbi.nlm.nih.gov/clinvar/variation/4033/

gnomAD: European (Non-Finnish) 1.880e-4, Overall 9.959e-5 http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

CaseAddInfo: Late Onset Pompe Disease

Case14: Female, 15 years onset, 16 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 16, GAA Activity at ~8 pmol/min/mg before ERT and ~12 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.1927G>A (p.Gly643Arg)

ClinVar: 4023 https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: European (Non-Finnish) 3.667e-5, Overall 2.479e-5 http://gnomad.broadinstitute.org/variant/17-78086713-G-A

CaseAddInfo: Late Onset Pompe Disease

Case#: Patient 7, female

CasePresentingHPOs: HP:0003236, HP:0003325

CaseAddInfo: 53yo at onset, 55yo 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.1927G>A (p.Gly643Arg)

ClinVar: 4023, https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: 5.884e-05, http://exac.broadinstitute.org/variant/17-78086713-G-A

Case#: Patient 15, female

CasePresentingHPOs: HP:0003236, HP:0003325

CaseAddInfo: 42yo at onset, 52yo 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.1927G>A (p.Gly643Arg)

ClinVar: 4023, https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: 5.884e-05, http://exac.broadinstitute.org/variant/17-78086713-G-A

Case10: Male, 80 years report

HPOsFreeText: 7 years of ERT completed, 6 Minute Walking Test at 220 meters, Forced Vital Capacity at 44%

GenotypingMethod: GAA Gene Sequencing

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

ClinVar: 4027 http://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.1927G>A (p.Gly643Arg)

ClinVar: 4023 https://www.ncbi.nlm.nih.gov/clinvar/variation/4023/

gnomAD: European (Non-Finnish) 3.667e-5, Overall 2.479e-5 http://gnomad.broadinstitute.org/variant/17-78086713-G-A

CaseAddInfo: Late Onset Pompe Disease

'Aroint thee, witch!' the rump-fed ronyon cries. at 4023..4071