Case6HPOsFreeText: 10 mg/kg GAA treatment, GAA activity at 1 pmol/punch/hr, GAA activity at 10% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

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 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2242dupG (p.Glu748Glyfs)

ClinVar: 370651 https://www.ncbi.nlm.nih.gov/clinvar/variation/370651/

gnomAD: European (Non-Finnish) 1.767e-5, Overall 7.975e-6 https://gnomad.broadinstitute.org/variant/17-78090813-T-TG

CaseAddInfo:

Case17HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 0.38 umol/g/h, GAA activity at 12.7% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

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 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2242dupG (p.Glu748Glyfs)

ClinVar: 370651 https://www.ncbi.nlm.nih.gov/clinvar/variation/370651/

gnomAD: European (Non-Finnish) 1.767e-5, Overall 7.975e-6 https://gnomad.broadinstitute.org/variant/17-78090813-T-TG

CaseAddInfo:

Case8HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 8 pmol/punch/hr, GAA activity at 33% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

CaseGenotypingMethod: Method not described, only that the diagnosis was "confirmed … based on 2 GAA gene mutations"

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 https://gnomad.broadinstitute.org/variant/17-78078341-T-G

Variant2: NM_000152.4:c.2242dupG (p.Glu748Glyfs)

ClinVar: 370651 https://www.ncbi.nlm.nih.gov/clinvar/variation/370651/

gnomAD: European (Non-Finnish) 1.767e-5, Overall 7.975e-6 https://gnomad.broadinstitute.org/variant/17-78090813-T-TG

CaseAddInfo:

Case71

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.2242dupG (p.Glu748Glyfs*48)

ClinVar: 370651 https://www.ncbi.nlm.nih.gov/clinvar/variation/370651/

gnomAD: European (Non-Finnish) 1.767e-5, Overall 7.975e-6 http://gnomad.broadinstitute.org/variant/17-78090813-T-TG

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

Patient20: Female, 46yo at diagnosis and ERT

CasePresentingHPOs:

HPOsFreeText: anti rh-GAA antibodies titre = 1:12,800, enzyme (μmol/g/h) = 0.64 (3-20), NIV required before and after ERT

CaseNotHPOs:

NotHPOsFreeText: mobility aid not required

CaseAddInfo: 26yr disease progression, variants in trans

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.2242dupG (p.Glu748Glyfs)

ClinVar: 370651, https://www.ncbi.nlm.nih.gov/clinvar/variation/370651/

gnomAD: 1.66e-05, http://exac.broadinstitute.org/variant/17-78090813-T-TG

Patient19: Male, 54yo at diagnosis and ERT

CasePresentingHPOs:

HPOsFreeText: anti rh-GAA antibodies titre = 1:6400, enzyme (μmol/g/h) = 0.41 (3-20), NIV and mobility aid required before and after ERT

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 35yr disease duration, variants in trans

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.2242dupG (p.Glu748Glyfs)

ClinVar: 370651, https://www.ncbi.nlm.nih.gov/clinvar/variation/370651/

gnomAD: 1.66e-05, http://exac.broadinstitute.org/variant/17-78090813-T-TG