Case5: Male, 0.8 yr onset, 2.3 yr diagnosis, 9.5 yr report

HPOsFreeText: FVC z-score sitting -1.53 (82% pred), FVC z-score supine -1.71 (80% pred), 98% MRC Scale, 550 CK U/l, 15.4 GAA activity (nmol/h/mg)^h from cultured fibroblasts

NotHPOsFreeText: No wheelchair used, No respiratory support

Case29: Female, 6.5 yr onset, 11.6 yr diagnosis, 12.7 yr report

CasePresentingHPOs: HP:0001371 (Contractures)

HPOsFreeText: FVC z-score sitting -2.36 (73% pred), FVC z-score supine -2.89 (67% pred), 79% MRC Scale, 776 CK U/l, 8.4 GAA activity (nmol/h/mg)^h from cultured fibroblasts

NotHPOsFreeText: No wheelchair used, No respiratory support

Case1: Male, 0.5 yr onset, 2.5 yr diagnosis, 10.04 yr report

CasePresentingHPOs: HP:0001371 (Contractures)

HPOsFreeText: Wheelchair used, FVC z-score sitting -0.25 (97% pred), FVC z-score supine -1.12 (87% pred), 65% MRC Scale, 530 CK U/l, 9.1 GAA activity (nmol/h/mg)^h from cultured fibroblasts

NotHPOsFreeText: No respiratory support

Case9: Male, 2 yr onset, 1 yr diagnosis, 6.6 yr report

HPOsFreeText: FVC z-score sitting -0.97 (89% pred), FVC z-score supine -1.4 (84% pred), 94% MRC Scale, 763 CK U/l, 11 GAA activity (nmol/h/mg)^h from cultured fibroblasts

NotHPOsFreeText: No wheelchair used, No respiratory support

Case9: Male, 5 yr onset, 10.8 yr diagnosis, 10.8 yr report

HPOsFreeText: FVC z-score sitting 0.2 (102% pred), FVC z-score supine -0.29 (97% pred), 97% MRC Scale, 588 CK U/l, 11.9 GAA activity (nmol/h/mg)^h from cultured fibroblasts

NotHPOsFreeText: No wheelchair used, No respiratory support

Case19: Male, 13.1 yr diagnosis, 13.1 yr report

HPOsFreeText: FVC z-score sitting -0.69 (92% pred), FVC z-score supine -1.77 (80% pred), 100% MRC Scale, 614 CK U/l, Deficent GAA activity (nmol/h/mg)^h from cultured fibroblasts

NotHPOsFreeText: No wheelchair used, No respiratory support

Case7: Male, 1 yr onset, 2 yr diagnosis, 13.7 yr report

CasePresentingHPOs: HP:0002650 (Scoliosis)

HPOsFreeText: Respiratory support at night, FVC z-score sitting -4.08 (54% pred), FVC z-score supine -5.4 (39% pred), 87% MRC Scale, 548 CK U/l, 17.9 GAA activity (nmol/h/mg)^h from cultured fibroblasts

NotHPOsFreeText: No wheelchair used

Case22: Male, 0.5 yr onset, 1 yr diagnosis, 1.3 yr report

HPOsFreeText: Wheelchair used at 4 yr, Died of respiratory failure at 10 yr, FVC z-score sitting -4.77 (45% pred) at 9 yr, 586 CK U/l, Deficient GAA activity (nmol/h/mg)^h from cultured fibroblasts

Case1: Male, 62 years report

CasePresentingHPOs: HP:0002091, HP:0002878, HP:0003701, HP:0040047, HP:0002098, HP:0100786, HP:0006510, HP:0005978, HP:0000822, HP:0003124, HP:0001677, HP:0003236, HP:0004324, HP:0002329, HP:0030207, HP:0002098, HP:0040047, HP:0100750, HP:0002097, HP:0007269, HP:0040046 (Restrictive lung disease, Respiratory failure, Proximal muscle weakness, Abnormality of the right hemidiaphragm, Shortness of breath, Hypersomnia, Chronic obstructive pulmonary disease, Diabetes mellitus Type II, Hypertension, Hypercholesterolemia, Coronary artery disease, Elevated serum creatine kinase, Increased body weight, Drowsiness, Paradoxical respiration, Respiratory distress, Abnormality of the right hemidiaphragm, Atelectasis, Emphysema, Spinal muscular atrophy, Abnormality of the left hemidiaphragm)

HPOsFreeText: Hypercapnic respiratory failure, Chronic phrenic neuropathy bilaterally, Long history of apparently idiopathic right hemidiaphragm paralysis, Underwent muscle biopsy and electromyography, both of which showed nonspecific myopathic features associated with mild denervation, On presentation, the patient's vital signs were a temperature of 36.5 °C (97.7 °F); heart rate, 94 beats/minute; blood pressure, 104/70 mm Hg; respiratory rate, 22 breaths/minute; oxygen saturation, 90% when receiving 2 L of supplemental oxygen per minute; and body mass index, 29.9 kg/m2, Decreased air entry bilaterally, Laboratory values were: Hemoglobin, 120 g/L; platelets, 279 × 109/L; white blood cells, 7.7 × 109/L; sodium, 140 mmol/L; potassium, 5.1 mmol/L; bicarbonate, 40 mmol/L; serum urea nitrogen, 3.6 mmol/L; creatinine, 70.7 μmol/L; and calcium, 2.48 mmol/L, Fatty atrophy of rotator cuff musculature, Tests for resting room-air arterial blood gases showed a pH of 7.29; PCO2, 89.4 mm Hg; PO2, 67.6 mm Hg; and serum bicarbonate, 43 mmol/L, Right diaphragm paralysis, Electromyography showed complete absence of phrenic compound muscle action potentials bilaterally. No activation of motor unit potentials was seen within the diaphragm, either with respiration or with volitional effort. Ultrasonography showed that the left hemidiaphragm was hyperechoic, 0.14 cm thick at functional residual capacity (FRC), with a thickening ratio of 1.1 (the thickening ratio is thickness at total lung capacity/thickness at FRC). The right hemidiaphragm was hyperechoic, 0.15 cm thick at FRC, with thickening ratio of 0.9. (Normal thickness is >0.15 cm, normal thickening ratio is >1.2.) The aldolase concentration was slightly increased at 9 U/L (reference level, <7.7 U/L). To complete the evaluation for rarer causes of diaphragmatic dysfunction, neurology services requested testing for inherited neuropathies. Three weeks later, the patient's serum GAA level was 1.0 nmol/mL/hour (reference level, >7.4 nmol/mL/hour)

CaseNotHPOs: HP:0003549 (Abnormality of connective tissue)

NotHPOsFreeText: The following tests were within reference range: creatine kinase, thyroid function tests, erythrocyte sedimentation rate, serum and protein electrophoresis, antinuclear antibody profile, and anti-Jo antibodies

CaseAddInfo: Ex-Smoker with 40–80 pack-years of smoking, Medications at presentation to facility included aspirin, clopidogrel, simvastatin, diltiazem, sitagliptin, metformin, budesonide and formoterol inhaler, tiotropium bromide inhaler, and albuterol inhaler

PatientF2P2: Female, 39 years diagnosis, Caucasian

CasePresentingHPOs: HP:0003323, HP:0003198, (Progressive muscle weakness, Myopathy)

HPOsFreeText: Had deficient muscle acid GAA activity (1.0 mmol/min/g, control >4.0 mmol/min/g)

CaseAddInfo: Mother of F2P1, the proband, who died at 8 months secondary to the disease.

PatientF1P4: Male, birth onset, prenatal diagnosis, Caucasian

HPOsFreeText: IOPD was confirmed with decreased acid GAA on a lymphocyte assay (6 nmol/hr/mg, control 36 nmol/hr/mg) and on a foreskin fibroblast sample,

CaseAddInfo: First cousin twice removed of F1P1, Mother carries both c.1880C>T and VUS c.1642G>T mutations in cis

Case3HPOsFreeText: 5 mg/kg GAA treatment, GAA activity at 3.1 pmol/punch/hr, GAA activity at 31% lower limit of normal

CaseAddInfo: Late Onset Pompe Disease

Case7HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 14 pmol/punch/hr, GAA activity at 58.3% 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.525delT (p.Glu176Argfs)

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

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

CaseAddInfo:

Case19HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 8 pmol/spot/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.525delT (p.Glu176Argfs)

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

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

CaseAddInfo:

Case12: Male, 35 years onset, 50 years diagnosis, 61 years report, France

CasePresentingHPOs: HP:0002540, HP:0002878, HP:0004887 (Inability to walk, Respiratory failure, Respiratory failure requiring assisted ventilation)

HPOsFreeText: Lost ambulation at 48 years, Started invasive ventilation at 35 years, Started ERT given every other week at a dose of 20 mg/kg at 56 years for 49 months, Peak Anti-rhGAA antibodies at 1:1600, FVC at 0 (L / % expected), MIP at 22 (cm H2O), MEP at 28 (cm H2O), Time off ventilation stayed constant at 0 min, 6MWT stayed constant at 0 meters

CaseNotHPOs: HP:0030148 (Heart murmur)

NotHPOsFreeText: No adverse reaction to ERT was recorded

CaseAddInfo: Late Onset Pompe Disease

Case3: Male, 28 years onset, 30 years diagnosis, 69 years report, France

CasePresentingHPOs: HP:0002540, HP:0002878, HP:0004887, HP:0002093 (Inability to walk, Respiratory failure, Respiratory failure requiring assisted ventilation, Respiratory insufficency)

HPOsFreeText: Lost ambulation at 58 years, Started invasive ventilation at 28 years, Started ERT given every other week at a dose of 20 mg/kg at 68 years for 11 months, Peak Anti-rhGAA antibodies at 1:1600, FVC at 0.45/13 (L / % expected), MIP at 17 (cm H2O), MEP at 29 (cm H2O), Time off ventilation stayed constant at 0, Total Motor Function Measure from 31 to 27

CaseNotHPOs: HP:0030148 (Heart murmur)

NotHPOsFreeText: No adverse reaction to ERT was recorded

CaseAddInfo: Late Onset Pompe Disease, Patient died before publication

Case1: Male, Caucasian, United States, Birth onset

CasePresentingHPOs: HP:0008872, HP:0002100, HP:0001508, HP:0008947, HP:0001655, HP:0003236, HP:0200136, HP:0001290, HP:0002835, HP:0002194 (Feeding difficulties in infancy, Recurrent aspiration pneumonia, Poor weight gain, Infantile muscular hypotonia, Patent foramen ovale, Increased serum CK, Oropharyngeal dysphagia, Low muscle tone, Aspiration, Delayed gross motor development)

HPOsFreeText: HyperCKemia was present since the early neonatal period (378 IU/L, day 8 of life; N: 60–305 IU/L), ERT at a dose of 20 mg/kg every 2 weeks was initiated at age 1 month, CK levels were normalized on ERT by age 4 months (80 IU/L), Flexion/abduction/ external rotation positioning of lower extremities, iliotibial (IT) band tightness, lack of independent sitting, AIMS score between 10th and 25th percentile, GMFM at 23.16%, At age 23 months, he had achieved significant motor milestones; started sitting with support at 10 months and without support at 12 months, pulled to stand at 12 months, walked at 15 months and could feed himself with an immature pincer grasp. Swallow study was normal, ALT 26 U/L (Normal 5–40 U/L), AST 45 U/L (Normal 15–41 U/L), ALP 211 U/L (Normal 24–170 U/L), Urinary Glc4 3.7 mmol/mol creatinine (Normal ≤8.3 mmol/mol creatinine)

CaseNotHPOs: HP:0011675, HP:0002910 (ECG abnormality, Elevated hepatic transaminases)

NotHPOsFreetext:

CaseAddInfo: Older brother of Patient 2, Late-Onset Pompe Disease

Case2: Male, Caucasian, United States, Birth onset

CasePresentingHPOs: HP:0001290, HP:0200136, HP:0002033, HP:0003236, HP:0001655, HP:0002058, HP:0002194, HP:0002421, HP:0000467, HP:0002015 (Generalized hypotonia, Oral-pharyngeal dysphagia, Poor suck, Increased serum CK, Patent foramen ovale, Myopathic face, Delayed gross motor development, Poor head control, Neck muscle weakness, Dysphagia)

HPOsFreeText: hyperCKemia at 435 IU/L on day of life 4, Patent foramen ovale detected at birth by ECHO but resolved spontaneously, PT evaluation at age 2 months revealed flexion/abduction/external rotation positioning of lower extremities with tightness bilaterally in hip flexors, hamstrings, and IT bands, Had a tendency to remain on toes when held in supported standing with additional support required for weight bearing through lower extremities, Had difficulty lifting his head in prone, with asymmetric head lift to 45 degrees, and an inability to maintain head in midline when supine, AIMS score at age 2 months was between 10–25th percentile, ALT 41 U/L (Normal 5–40 U/L), AST 33 U/L (Normal 15–41 U/L), ALP 239 U/L (Normal 24–170 U/L), Urinary Glc4 4.5 mmol/mol creatinine (Normal ≤8.3 mmol/mol creatinine)

CaseNotHPOs: HP:0011016 (Abnormality of urine glucose concentration)

NotHPOsFreeText:

CaseAddInfo: Younger brother of Patient 1, Late-Onset Pompe Disease

Case9: Male, 46 years onset, 48 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 48, 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

Case8: Male, 16 years onset, 36 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 36, GAA Activity at ~5 pmol/min/mg before ERT and ~13 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

Case13: Male, 34 years onset, 45 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 45, GAA Activity at ~10 pmol/min/mg before ERT and ~10.5 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

Case11: Female, 48 years onset, 54 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 54, GAA Activity at ~8.5 pmol/min/mg before ERT and ~9 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

Case5: Male, 65 years onset, 72 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 72, GAA Activity at ~6 pmol/min/mg before ERT and ~10.5 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

Case#: Patient (case report), male, 1 month old, ethnicity unknown

DiseaseAssertion: Pompe disease

FamilyInfo: No history of consanguinity in parents. The patient has a 15 months old sibling that is healthy.

Family medical history was notable for tuberous sclerosis in the patient’s father’s first cousin.

CasePresentingHPOs: HP:0200128, HP:0001639, HP:0002240

(Biventricular hypertrophy, Hypertrophic cardiomyopathy, Hepatomegaly,

CaseHPOFreeText: Echogenic mass within the left ventricle.

Short-axis images revealed the possibility of an additional mass within the left ventricle adjacent to the papillary muscles

Right axis deviation

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

Normal results were noted for levels of plasma amino acids, lactate and pyruvate, total and free carnitine, and acylcarnitine compounds. Urine organic acid quantitation was normal.

PR interval was normal

CasePreviousTesting: The serum creatine kinase was elevated (478 U/L; normal 60–305 U/L).

GAA activity in whole blood from a blood spot was 1.8 pmol/punch/hour (control 10–49 pmol/punch/hour)

The GAA gene was sequenced.

Variant 1: NM_000152.5(GAA):c.525del (p.Glu176fs)

ClinVar: 4033

CAID: CA220406

gnomAD: N/A

Variant 2: NM_000152.5(GAA):c.1927G>A (p.Gly643Arg)

ClinVar: 4023

CAID: CA116596

gnomAD: Highest population MAF=0.00003667 (Euroean (non-Finnish))

ParentalGenotype:N/A

PreviouslyPublished:N/A

Patient20: Male, 19yo

CasePresentingHPOs:

HPOsFreeText: LOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 19yr disease duration, ERT lasted 132mo

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.525delT (p.Glu176Argfs)

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

gnomAD: 0.00009959, http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

Patient12: Female, 66yo

CasePresentingHPOs: HP:0003077, HP:0000822

HPOsFreeText: LOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 7yr disease duration, ERT lasted 33mo

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.525delT (p.Glu176Argfs)

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

gnomAD: 0.00009959, http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

Case# Patient 2, male

CasePresentingHPOs: HP:0003236, HP:0003325

CaseAddInfo: 66 at onset, 72 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.525delT (p.Glu176Argfs)

ClinVar: 4033

gnomAD: 7.041e-05, http://exac.broadinstitute.org/variant/17-78078909-CT-C

Case#: Patient 5, female

CasePresentingHPOs: HP:0003236, HP:0003325

CaseAddInfo: 64yo at onset, 67yo 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

Variant2Allele: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

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

gnomAD: 7.041e-05, http://exac.broadinstitute.org/variant/17-78078909-CT-C

Case46

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.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

Variant2: NM_000152.4:c.1655T>C (p.Leu552Pro)

ClinVar: 279811 https://www.ncbi.nlm.nih.gov/clinvar/variation/279811/

gnomAD: European (Non-Finnish) 7.053e-5, Overall 3.188e-5 http://gnomad.broadinstitute.org/variant/17-78085800-T-C

CaseAddInfo: Infantile Onset Pompe Disease

Case45

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.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

Variant2: NM_000152.4:c.1880C>T (p.Ser627Phe)

CAID: CA294896504 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1880C%3ET

gnomAD: Not in gnomAD

CaseAddInfo: Infantile Onset Pompe Disease

Case79

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.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

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, 3 other patients have the same genotype

Case44

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.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

Variant2: NM_000152.4:c.1799G>T (p.Arg600Leu)

CAID: CA401369428 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1799G%3ET

gnomAD: Not in gnomAD

CaseAddInfo: Infantile Onset Pompe Disease

Case51

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.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

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: Infantile Onset Pompe Disease

Case39

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.525delT (p.Glu176Argfs*45)

CAID: 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: Infantile Onset Pompe Disease, 1 more patient has the same genotype

Case11: Male, 57 years report

HPOsFreeText: 9 years of ERT completed, 6 Minute Walking Test at 210 meters, Forced Vital Capacity at 31%

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.525delT (p.Glu176Argfs*42)

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

Case13: Female, 30 years report

HPOsFreeText: 7 years of ERT completed, 6 Minute Walking Test at 520 meters, Forced Vital Capacity at 50%

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.525delT (p.Glu176Argfs*42)

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

Case1: Female, 33 years onset, 35 years report

CasePresentingHPOs: HP:0030148, HP:0002094, HP:0001644, HP:0001712, HP:0006673, HP:0025168, HP:0030718, HP:0031295, HP:0001667, HP:0012667, HP:0006673, HP:0031185, HP:0002150, HP:0003165, HP:0008200, HP:0008208, HP:0002375, HP:0030232, HP:0004356, HP:0001685, HP:0040014, HP:0100295, HP:0001297 (Cardiac murmur, Dyspnea, Dilated cardiomyopathy, Left ventricular hypertrophy, Reduced systolic function, Left ventricular diastolic dysfunction, Right atrial enlargement, Left atrial enlargement, Right ventricular hypertrophy, Regional left ventricular wall motion abnormality, Reduced systolic function, Increased NT-proBNP level, Hypercalciuria, Elevated serum PTH, Primary hyperparathyroidism, Parathyroid hyperplasia, Hypokinesia, Increased sarcoplasmic glycogen, Abnormality of lysosomal metabolism, Myocardial fibrosis, Increased mitochondrial number, Muscle fiber atrophy, Stroke)

HPOsFreeText: At 33 years patient had left ventricular ejection fraction (LVEF) of 35% (normal 54–76%), while 7 months later she had LV volume of 81 ml (systolic) and 127 ml (diastolic), LV mass index (2D) of 141 g/m2; LV septum thickness of 12 mm (normal 7–10 mm); LV posterior wall thickness of 9 mm (normal 7–11 mm); end-diastolic LV diameter of 55 mm (normal 39–53 mm), and LVEF of 34% and Liver longitudinal peak systolic strain of ~8% (normal < −18%); A subsequent MRI confirmed an LVEF of 32% (normal 54–85%), LV volume/Body Surface Area (BSA) of 91 ml/m2 (systolic, normal 12–36 ml/m2) and 134 ml/m2 (diastolic, normal 49–90 ml/m2), and LV mass/BSA of 66 g/m2 (diastolic, normal 59–103 g/m2); Extensive biventricular delayed myocardial enhancement predominantly in the epicardial and transmural muscles was noted; Pro-BNP level was elevated to 3,894 pg/ml; Histologic analysis of formalin-fixed tissue revealed prominent myocyte vacuolization that were dilled with glycogen; GAA activity was measured twice in dried blood spots - once with carrier levels and once with affected levels, however the GAA activity in skin fibroblasts (16.7% normal: 260±80 nmol/h/mg protein) and in heart biopsy tissue (0.07; normal: 0.89±0.42 μmol/min/g tissue) was clearly in the affected range and partially reduced in the muscle biopsy tissues (5.86; 38% of normal: 22.91±8.4 nmol/h/mg protein); Both muscle and heart tissue glycogen content and structure tested in the low or normal ranges (muscle glycogen content 0.11 umol glucose/mg tissue; normal 0.39–1.5; muscle glycogen structure measured as glucose-1-phosphate/glucose ratio 72.22%; normal > 5%; heart glycogen content 0.14 umol glucose/mg tissue; normal > 0.047; and heart glycogen structure 23.91%; normal > 5%); Urine glucose tetrasaccharides biomarker level was normal at 1.0 mmol/mol cr (<4); The patient was also noted to have elevation of calcium (11.6 mg/dl, reference 8.9–10.1 mg/dl) and PTH (541 pg/ml, reference 15–65 pg/ml); Skeletal muscle biopsy showed denervation atrophy; Several months after LVEF declined to 20–25% (normal 54–76%) with CK-MB being 36 U/l (normal 7.0–25.0 U/l); Patient had slightly weak back extensors and her 6-min walk test showed 76.9% predicted for her age and gender

CaseNotHPOs: HP:0040081, HP:0002792, HP:0001324, HP:0002167, HP:0000157 (Abnormal levels of creatine kinase in blood, Reduced vital capacity, Muscle weakness, Speech impairment, Lingual abnormality)

NotHPOsFreeText: Branching enzyme activity in the heart and muscle tissue was normal; Phosphofructokinase and myophosphorylase enzymatic activities were intact

CaseAddInfo: No family history of cardiomyopathy or sudden death

Patient10: male, 18yo, juvenile onset

CasePresentingHPOs:

HPOsFreeText: LOPD, BMI = 15.2 / 16.5 / n-a, WGMS = 0 / 0 /n-a

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.525delT (p.Glu176Argfs)

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

gnomAD: 0.00009959, http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

Patient5: female, 53yo, adult onset

CasePresentingHPOs:

HPOsFreeText: LOPD, BMI = 21.1 / 21.1 / 22.5, WGMS = 3 / 3 / 3

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.525delT (p.Glu176Argfs)

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

gnomAD: 0.00009959, http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

Case#: Patient 4, Female, 10 days old at diagnosis, African American

DiseaseAssertion: Pompe disease

FamilyInfo:N/A

CasePresentingHPOs: HP:0009062, HP:0001638

(Infantile axial hypotonia, Cardiomyopathy)

CaseHPOFreeText: Before ERT patient withdraws extremities to stimulation, contractures of large joint of upper and lower extremities, weak grasp. Also patient was invasively ventilated. Baseline – G-tube feeds and continues

Currently patient is off ventilator 10-12 hours a day. Sits with support; and has minimal capacity for weight bearing on lower extremities. G tube feed.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: No GAA measurement

Variant 1: M_000152.5(GAA):c.525del (p.Glu176fs)

ClinVar: 4033

CAID: CA220406

gnomAD: N/A

Variant 2: NM_000152.5(GAA):c.2560C>T (p.Arg854Ter)

ClinVar: 4034

CAID: CA340130

gnomAD: Highest population MAF= 0.001891 (African)

ParentalGenotype:N/A

PreviouslyPublished:N/A

Patient18: female, White British

CasePresentingHPOs: HP:0003677, HP:0003236, HP:0003325, HP:0003701, HP:0003458, HP:0003715, HP:0030231

HPOsFreeText: CK > 10x increase, CK = 599 U/L. Vacuolated, degenerated, and atrophic fibers. Vacuole periphery showed abnormal immunoreactivity for desmin and p62. Z-band streaming of fibers, granular material accumulation. Treated with ERT. Normal to low alpha-glucosidase activity.

CaseNotHPOs: HP:0002093

NotHPOsFreeText: no evidence of glycogenosis

CaseAddInfo: onset after 50yo

CasePreviousTesting: same as group, muscle biopsy, NADH-tetrazolim reductase staining

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

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

gnomAD: 7.041e-05, http://exac.broadinstitute.org/variant/17-78078909-CT-C

Variant2: 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

Patient32: Male, Caucasian, first investigated at 15yo

CasePresentingHPOs: HP:0003677, HP:0002111, HP:0002875, HP:0003458

HPOsFreeText: CK < 10x increase, CK = 662 U/L. Reduced alpha-glucosidase activity.

CaseNotHPOs: HP:0003325, HP:0002093

CaseAddInfo: onset in childhood, confirmed Pompe Disease via Sanger Sequencing, 2 siblings also carried same variants and presented with reduced enzyme activity but were asymptomatic at time of study.

CasePreviousTesting: same as group, muscle biopsy, EMG

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

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

gnomAD: 7.041e-05, http://exac.broadinstitute.org/variant/17-78078909-CT-C

Variant2: 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

Case#: Patient 2, male, symptoms noticed at 5 months

DiseaseAssertion: Pompe Disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639, HP:0001324 (hypertrophic cardiomyopathy, muscle weakness)

CaseHPOFreeText: Inability to swallow (needed NGT feeding until 21 months old)

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: <1% normal GAA expression in fibroblast; after ERT treatment had 100% enzyme activity in cell lysates; unclear how patient was diagnosed

Variant 1: NM_000152.5:c.525delT

Variant 1 ClinVarID: 4033

Variant 1 CAid: CA220406

Variant 2: NM_000152.5:c.525delT

Variant 2 ClinVarID: 4033

Variant 2 CAid: CA220406

ParentalGenotype: Not provided

Case#: Patient 3, female, symptoms began at birth, diagnosed at 5 weeks

DiseaseAssertion: Pompe Disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001639, HP:0003712 (hypertrophic cardiomyopathy, hypertrophy of calves)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: <1% normal GAA expression in fibroblast; after ERT treatment had 100% enzyme activity in cell lysates; unclear how patient was diagnosed

Variant 1: NM_000152.5:c.525delT

Variant 1 ClinVarID: 4033

Variant 1 CAid: CA220406

Variant 2: NM_000152.5:c.525delT

Variant 2 ClinVarID: 4033

Variant 2 CAid: CA220406

ParentalGenotype: Not provided

Case#: Subject number 2(I), male, 10 days (start of ERT)

DiseaseAssertion: Infantile Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0200128 (biventricular hypertrophy), HP:0005165 (shortened PR interval), HP:0030234 (Highly elevated creatine kinase), HP:0001270 (motor delay)

CaseHPOFreeText: severe septal left ventricular hypertrophy and mildly hypertrophied right ventricle. CRIM positive.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 846 U/L (60–305 U/L is normal), AST: 189 U/L (30–100 U/L is normal), ALT: 91 U/L (7-50 U/L is normal), BNP: 1232.5 pg/mL (0.0–100.0 pg/mL), Hex4: 30.2 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 0.65 micromole/L/h and GAA activity #2 (NBS) 0.34 in dried blood spots (>2.10 micromole/L/h is normal). 0.4 in confirmatory testing (<3.88 is normal).

Variant 1: NM_000152.5(GAA):c.525delT

Variant 1 ClinVarID: 4033

Variant 1 CAid: CA220406

Variant 2: NM_000152.5(GAA):c.1694_1697delTCTC

Variant 2 ClinVarID: N/A

Variant 2 CAid: CA658795263

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Patient3: Male, 1.2mo at ERT start, 5.5yo at study end

CasePresentingHPOs:

HPOsFreeText: treated with 20mg/kg/2wks, patient had 27 infusion associated reactions

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.1933G>T (p.Asp645Tyr)

ClinVar: 556386, https://www.ncbi.nlm.nih.gov/clinvar/variation/556386/

gnomAD: 0.000008250, http://gnomad.broadinstitute.org/variant/17-78086719-G-T

Variant2: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

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

gnomAD: 0.00009959, http://gnomad.broadinstitute.org/variant/17-78078909-CT-C

Patient1: control experiment performed on patient's primary fibroblasts to validate U7 snRNA vector, screen showed multiple U7 snRNA-based AONs that modulate inclusion of exon 2 in GAA mRNA

CasePresentingHPOs:

HPOsFreeText: LOPD

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: n/a

CaseGenotypingMethod: n/a

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.525delT (p.Glu176Argfs)

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

gnomAD: 7.041e-05, http://exac.broadinstitute.org/variant/17-78078909-CT-C

Case6: Female, French, 26 years report, 21 years onset

CasePresentingHPOs: HP:0008956 (Thigh muscle atrophy)

HPOsFreeText: 6-min walk test achieved 496 m, MRC score is 3/5 (thigh/calf), Forced vital capacity sitting/supine is 2.2/1.9 (L), Has started ERT,On the medication Perindopril

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.525delT (p.Glu176Argfs)

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

Case22: Male, 16 years onset, 41 years diagnosis

CaseAddInfo: Late-Onset Pompe Disease

Case#: Patient 1, woman, 58 years old, ethnicity unknown

DiseaseAssertion:Pompe disease

Was also misdiagnosed with adult-onset spinal muscular atrophy (SMA)

FamilyInfo: No family history of muscle disease

CasePresentingHPOs: HP:0003701, HP:0100284

(Proximal muscle weakness, EMG myotonic discharges)

CaseHPOFreeText: Denervation atrophy from a muscle biopsy

Weakness of hip flexion 2–3/5, hip abduction 2/5, and hip adduction 2/5

Myotonic discharges were in the lumbar paraspinals, vastus medialis, and tensor fasciae latae muscles.

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: GAA enzyme activity assay was 1 pmol/punch/h (normal range 10–49 pmol/punch/h)

Her creatine kinase (CK) level at presentation had been elevated as high as 429 U/L (normal range 45–145)

Found with two mutations in the GAA gene

Variant: NM_000152.5(GAA):c.-32-13T>G

ClinVar: 4027

CAID: CA116606

gnomAD: Highest population MAF= 0.005541 (Ashkenazi Jewish)

Variant: NM_000152.5(GAA):c.525del (p.Glu176fs) Double check this variant

ClinVar: 4033

CAID: CA220406

gnomAD: N/A

ParentalGenotype:N/A

Previously Published: N/A

Case#: Patient 4, male, diagnosed 2015 (not given age of diagnosis), age 42 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 (unclear variant nomenclature)

Variant 1 ClinVarID: N/A

Variant 1 CAid: CA913184742

Variant 2: NM_000152.5:c.525del

Variant 2 ClinVarID: 4033

Variant 2 CAid: CA220406

ParentalGenotype: Not provided

Patient7: Female, 49yo at diagnosis, 50yo at ERT

CasePresentingHPOs:

HPOsFreeText: anti rh-GAA antibodies titre = 1:1600, enzyme (μmol/g/h) = 0.78 (3-20)

CaseNotHPOs:

NotHPOsFreeText: NIV and mobility aid not required

CaseAddInfo: 25yr 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.525delT (p.Glu176Argfs)

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

gnomAD: 7.041e-05, http://exac.broadinstitute.org/variant/17-78078909-CT-C

Patient3: Male, Caucasian, 11yo

CasePresentingHPOs:

HPOsFreeText: IOPD, negative rhGAA IgG antibody titer, CRIM positive

CaseNotHPOs:

NotHPOsFreeText: no infusion associated reactions

CaseAddInfo: diagnosed at birth, 15days old at ERT start

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.4(GAA):c.525delT (p.Glu176Argfs)

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

gnomAD: 0.00009959, https://gnomad.broadinstitute.org/variant/17-78078909-CT-C

Variant2: NM_000152.5(GAA):c.1642G>T (p.Val548Phe)

ClinVar: 5973381, https://www.ncbi.nlm.nih.gov/clinvar/variation/597381/

gnomAD: n/a

Variant3: NM_000152.5(GAA):c.1880C>T (p.Ser627Phe)

ClinVar: 597382, https://www.ncbi.nlm.nih.gov/clinvar/variation/597382/

gnomAD: n/a