Case18: Male, 4 yr diagnosis, 5.2 yr report

HPOsFreeText: FVC z-score sitting -1.41 (82% pred), FVC z-score supine -1.96 (76% pred), 97% MRC Scale, 677 CK U/l, Deficent GAA activity (nmol/h/mg)^h from cultured fibroblasts

NotHPOsFreeText: No wheelchair used, No respiratory support

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

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

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

Case25: Male, 2.7 yr onset, 3.5 yr diagnosis, 5.9 yr report

HPOsFreeText: FVC z-score sitting 0.34 (104% pred), FVC z-score supine 0.04 (100% pred), 87% MRC Scale, 908 CK U/l, 2.8 GAA activity (nmol/h/mg)^h from cultured fibroblasts

NotHPOsFreeText: No wheelchair used, No respiratory support

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

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

Case3: Female, 0.8 yr onset, 1.1 yr diagnosis, 8.9 yr report

CasePresentingHPOs: HP:0005165 (Shortened PR interval)

HPOsFreeText: FVC z-score sitting 0.21 (102% pred), FVC z-score supine 0.1 (101% pred), 358 CK U/l, 13.3 GAA activity (nmol/h/mg)^h from cultured fibroblasts, ECG showed delta wave suggestive of Wolff-Parkinson-White syndrome

NotHPOsFreeText: No wheelchair used, no respiratory support

Case5: Female, Caucasian, United States, 2 months onset and diagnosis, 0.4 years report

CasePresentingHPOs: HP:0011968, HP:0011469, HP:0012378, HP:0004347, HP:0010453 (Feeding difficulties, Nasal regurgitation, Fatigue, Weakness of muscles of respiration, Pelvic bone asymmetry)

HPOsFreeText: Difficulty in lying supine while eating, sleeping and self-limited gasping episodes was observed, PT evaluation showed mild consistent asymmetry with increased lateral head tilt to the right, Tendency towards flexion/abduction/external rotation positioning of lower extremities was noted, Slight lateral thigh grooves reflected early IT band tightness with decreased posterior weight shift and propping on forearms in prone, AIMS score was at 10th percentile for chronological age and 25th to 50th percentile for corrected age, ALT 27 U/L (Normal 5–40 U/L), AST 36 U/L (Normal 15–41 U/L), ALP 352 U/L (Normal 24–170 U/L), Urinary Glc4 4.1 mmol/mol creatinine (Normal ≤8.3 mmol/mol creatinine)

CaseNotHPOs: HP:0002033, HP:0002015, HP:0004323, HP:0003808 (Poor suck, Poor swallowing, Abnormality of body weight, Abnormal muscle tone)

NotHPOsFreeText: CK levels, ECG, and ECHO have consistently been within normal limits, Had normal passive ranges of motion and appropriate weight bearing through lower extremities in supported standing

Case4: Female, Caucasian, United States, 1 month onset, 6 months diagnosis, 1.1 years report

CasePresentingHPOs: HP:0003236, HP:0012378, HP:0006589, HP:0003725 (Increased serum CK, Fatigue, Flaring of lower rib cage, Firm muscles)

HPOsFreeText: HyperCKemia present in the first month (505 IU/L; Normal 30–279 IU/L) but normalized spontaneously at 4 months (188 IU/L), PT assessment revealed subtle motor signs including preferred position of ring sitting with hips in flexion/abduction/external rotation and bilateral IT band tightness, Imbalanced trunk flexion, Decreased use of abdominals and excessive use of spinal extension, Asymmetry was noted in reaching objects in prone and weight shifting with lateral flexion and shortening on the left at the neck and trunk, AIMS score was at the 25th percentile and GMFM was 22.14%, Urinary Glc4 4.8 mmol/mol creatinine (Normal ≤8.3 mmol/mol creatinine)

CaseNotHPOs: HP:0003690 (Limb muscle weakness)

NotHPOsFreeText: She had no head lag when pulled to sit and the ability to transfer objects and bring them to midline

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

Case7: Female, Caucasian, United States, 6 months diagnosis, 8 months report

CasePresentingHPOs: HP:0001643, HP:0006699, HP:0006682, HP:0003722, HP:0008969 (Patent ductus arteriosus, Premature atrial contractions, Premature ventricular contractions, Neck flexor weakness, Leg muscle stiffness)

HPOsFreeText: At 6 months head lag during pull to sit was noted, Had predominant overall flexion position of lower extremities with a tendency towards hip flexion/abduction/external rotation, with lateral thigh grooves suggestive of bilateral IT band tightness, AIMS score was between 10th and 25th percentile for chronological age and 50th percentile for her corrected age adjusted for prematurity while GMFM score was 16.55%, ALT 37 U/L (Normal 5–40 U/L), AST 53 U/L (Normal 15–41 U/L), ALP 174 U/L (Normal 24–170 U/L)

CaseNotHPOs: HP:0003236, HP:0001712, HP:0001290 (Increased serum CK, Left ventricular hypertrophy, Decreased muscle tone)

NotHPOsFreeText: Other evaluations including pulmonary, speech, and swallow were normal

Case6: Male, Caucasian, United States, 1 month onset, 6 months diagnosis, 8 months report

CasePresentingHPOs: HP:0003236, HP:0001655, HP:0003701, HP:0006589, HP:0003093, (Increased serum CK, Patent foramen ovale, Proximal muscle weakness, Flaring of lower rib cage, Limited hip extension,

HPOsFreeText: HyperCKemia was noticed in the first month (438 U/L; Normal 60–305) but normalized spontaneously by age 6 months, flexion/abduction/external rotation positioning of lower extremities and with bilateral IT band tightness was revealed at the same time, also had decreased active use of abdominal oblique muscles with a lack of active trunk rotation, Decreased active use of lower abdominal muscles with inability to achieve a posterior pelvic tilt in supine, AIMS score was at 1st percentile for age and GMFM was at 12.3%, ALT 30 U/L (Normal 5–40 U/L), AST 90 U/L (Normal 15–41 U/L), ALP 249 U/L (Normal 24–170 U/L), Urinary Glc4 2.6 mmol/mol creatinine (Normal ≤8.3 mmol/mol creatinine)

CaseNotHPOs: HP:0001712, HP:0001290 (Left ventricular hypertrophy, Decreased muscle tone)

NotHPOsFreeText: Other evaluations including cardiac, pulmonary, speech, and swallow were normal

Case1: Female, 55 years report, 25 years onset, Brazil, African

CasePresentingHPOs: HP:0003325, HP:0003236, HP:0003148, HP:0100284, HP:0011807, HP:0003326, HP:0008994, HP:0002527, HP:0003551, HP:0002015, HP:0000822, HP:0000819, HP:0003119, HP:0003707, HP:0003391, HP:0003327, HP:0001315, HP:0002515, HP:0010546 (Limb-girlde muscle weakness, Increased serum CK, Elevated serum acid phosphatase, EMG: myotonic discharges, Type 1 muscle fiber atrophy, Myalgia, Proximal muscle weakness in lower limbs, Falls, Difficulty climbing stairs, Dysphagia, Hypertension, Diabetes mellitus, Dyslipidemia, Calf muscle pseudohypertrophy, Gowers sign, Axial muscle weakness, Reduced deep tendon reflexes, Waddling gait, Muscle fibrillation)

HPOsFreeText: Serum CK 1467 U/L (normal: ≤ 200U/L), NaG/AaGIA ratio 40.4, %INH 87.2, GAA activity 4.2% from dried blood spot, Falls occurring mainly when walking for long distances, Normal Mini-Mental State Examination score (27/30), Mild symmetrical weakness in proximal muscles in the lower limbs (Medical Research Council grade 4), Needle electromyography revealed motor unit potentials with low amplitude and short duration in the iliopsoas muscle associated with fibrillation and short myotonic discharge potentials in lumbar paraspinal muscles

CaseNotHPOs: HP:0001270 (Motor delay)

NotHPOsFreeText: Muscle biopsy with the absence of vacuolar myopathy

CaseAddInfo: Late-Onset Pompe Disease, One sister diagnosed with LOPD based on low GAA activity and shared genetic variants but no other known relatives with the condition

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

Case3: Male, 19 years report, Italy

CasePresentingHPOs: HP:0003551 (Difficulty climbing stairs)

HPOsFreeText: Height is 1.78 m, Weight is 60 kg, BMI is 18.9 kg/cm2, 7 years on ERT, Forced Vital Capacity at 107%

CaseNotHPOs: HP:0002098 (Respiratory distress)

NotHPOsFreeText: Nocturnal non-invasive ventilation

CaseAddInfo: Late Onset Pompe Disease

Case11: Female, 16 years report, Italy

HPOsFreeText: Height is 1.62 m, Weight is 57 kg, BMI is 21.7 kg/cm2, 7 years on ERT, Forced Vital Capacity at 102%

CaseNotHPOs: HP:0002098 (Respiratory distress)

NotHPOsFreeText: Nocturnal non-invasive ventilation

CaseAddInfo: Late Onset Pompe Disease

Case4: Male, 17 years report, Italy

HPOsFreeText: Height is 1.88 m, Weight is 66 kg, BMI is 18.7 kg/cm2, 7 years on ERT, Forced Vital Capacity at 91%

CaseNotHPOs: HP:0002098 (Respiratory distress)

NotHPOsFreeText: Nocturnal non-invasive ventilation

CaseAddInfo: Late Onset Pompe Disease

Case6: Male, 21 years report, Italy

HPOsFreeText: Height is 1.74 m, Weight is 71 kg, BMI is 23.5 kg/cm2, 7 years on ERT, Forced Vital Capacity at 99%

CaseNotHPOs: HP:0002098 (Respiratory distress)

NotHPOsFreeText: Nocturnal non-invasive ventilation

CaseAddInfo: Late Onset Pompe Disease

Case1: Female, 46 years report, Italy

CasePresentingHPOs: HP:0003551 (Difficulty climbing stairs)

HPOsFreeText: Height is 1.64 m, Weight is 50 kg, BMI is 18.6 kg/cm2, 2 years on ERT, Forced Vital Capacity at 108%

CaseNotHPOs: HP:0002098 (Respiratory distress)

NotHPOsFreeText: Nocturnal non-invasive ventilation

CaseAddInfo: Late Onset Pompe Disease

Case8: Male, 53 years report, Italy

CasePresentingHPOs: HP:0003551, HP:0002098 (Difficulty climbing stairs, Respiratory distress)

HPOsFreeText: Height is 1.85 m, Weight is 106 kg, BMI is 31.0 kg/cm2, 7 years on ERT, Forced Vital Capacity at 55%, Nocturnal non-invasive ventilation

CaseAddInfo: Late Onset Pompe Disease

Case2: Male, 47 years report, Italy

HPOsFreeText: Height is 1.90 m, Weight is 112 kg, BMI is 31.0 kg/cm2, 4 years on ERT, Forced Vital Capacity at 112%

CaseNotHPOs: HP:0002098 (Respiratory distress)

NotHPOsFreeText: Nocturnal non-invasive ventilation

CaseAddInfo: Late Onset Pompe Disease

CaseII: Adult onset, 71 years diagnosis

CasePresentingHPOs: HP:0003701, HP:0003326, HP:0003236, HP:0003198 (Proximal muscle weakness, Myalgia, Increased serum CK, Myopathy)

HPOsFreeText: Plasma CK 5–10× Normal, GAA activity from dried blood spot: 0%, 6-Minute Walking Test: 40 min, Forced Vital Capacity Seated: 850 (22%)

CaseNotHPOs: HP:0002795 (Abnormal respiration)

CaseAddInfo: Late-Onset Pompe Disease

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

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

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

CaseI: Early adult onset, 49 years diagnosis

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

HPOsFreeText: Plasma CK 5–10× Normal, GAA activity from lymphocytes: 14.2%

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

CaseVI,2: Adult onset, 61 years diagnosis

CasePresentingHPOs: HP:0003701, HP:0002795, HP:0003388, HP:0003236, HP:0003198 (Proximal muscle weakness, Abnormal respiration, Easy fatiguability, Increased serum CK, Myopathy)

HPOsFreeText: GAA activity from dried blood spot: 0.22%, Forced Vital Capacity Seated: 2040 (46%), 6-Minute Walking Test: 418 min, Plasma CK 2.5-5x Normal

CaseAddInfo: Late-Onset Pompe Disease

Case9: Male, 40 years onset, 45 years diagnosis, 74 years report, France

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

HPOsFreeText: Lost ambulation at 50 years, Started invasive ventilation at 67 years, Started ERT given every other week at a dose of 20 mg/kg at 70 years for 43 months, Peak Anti-rhGAA antibodies at 1:409,600, Time off ventilation stayed constant at 0 min, Total Motor Function Measure from 29 to 26, 6MWT stayed constant at 0 meters

CaseNotHPOs: HP:0030148 (Heart murmur)

NotHPOsFreeText: No adverse reaction to ERT was recorded

CaseAddInfo: Late Onset Pompe Disease

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

Case7: Female, 3 years onset, 3 years diagnosis, 27 years report, France

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

HPOsFreeText: Lost ambulation at 11 years, Started invasive ventilation at 11 years, Started ERT given every other week at a dose of 20 mg/kg at 18 years for 114 months, Peak Anti-rhGAA antibodies at 1:102,400, FVC at 0.22/6 (L / % expected), MIP at 10 (cm H2O), MEP at 10 (cm H2O), Time off ventilation stayed constant at 0 min, Total Motor Function Measure from 23 to 19, 6MWT stayed constant at 0 meters

CaseNotHPOs: HP:0030148 (Heart murmur)

NotHPOsFreeText: No adverse reaction to ERT was recorded

CaseAddInfo: Late Onset Pompe Disease

Case4: Female, 20 years onset, 48 years diagnosis, 57 years report, France

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

HPOsFreeText: Lost ambulation at 42 years, Started invasive ventilation at 32 years, Started ERT given every other week at a dose of 20 mg/kg at 50 years for 87 months, Peak Anti-rhGAA antibodies at 1:25,600, FVC at 0.42/13 (L / % expected), MIP at 15 (cm H2O), MEP at 17 (cm H2O), Time off ventilation increased from 60 to 120 min, Total Motor Function Measure from 45 to 49, 6MWT from 10 to 30 meters

CaseNotHPOs: HP:0030148 (Heart murmur)

NotHPOsFreeText: No adverse reaction to ERT was recorded

CaseAddInfo: Late Onset Pompe Disease

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

Case1: Male, 21 years onset, 27 years diagnosis, 36 years report

CasePresentingHPOs: HP:0003325, HP:0003327, HP:0003236 (Limb-girdle muscle weakness, Axial muscle weakness, Increased serum CK)

CaseAddInfo: Late-Onset Pompe Disease

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

CaseA: Male, 10 months onset, 18 months diagnosis

CaseAPresentingHPOs: HP:0001270, HP:0003324 (Motor delay, Generalized weakness)

HPOsFreeText: CRIM positive

CaseNotHPOs: HP:0100543 (Cognitive impairment)

CaseAddInfo: Infantile-Onset Pompe Disease

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

Case8: Female, 18 years onset, 18.5 years diagnosis, 29 years report

CasePresentingHPOs: HP:0003325, HP:0003236 (Limb-girdle muscle weakness, Increased serum CK)

CaseAddInfo: Late-Onset Pompe Disease

Case14: Male, 28 years onset, 36 years diagnosis, 37 years report

CasePresentingHPOs: HP:0003325, HP:0003327, HP:0003236, HP:0003691 (Limb-girdle muscle weakness, Axial muscle weakness, Increased serum CK, Scapula alata)

CaseAddInfo: Late-Onset Pompe Disease

Case10: Female, 47 years onset, 50 years diagnosis, 64 years report

CasePresentingHPOs: HP:0003325, HP:0003236 (Limb-girdle muscle weakness, Increased serum CK)

CaseAddInfo: Late-Onset Pompe Disease

Case3: Female, 18 years onset, 19 years diagnosis, 26 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

Case17: Female, 40 years onset, 68 years diagnosis, 69 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

Case12: Male, 15 years onset, 40 years diagnosis

CaseAddInfo: Late-Onset Pompe Disease

Case15: Female, 13 years onset, 43 years diagnosis

CaseAddInfo: Late-Onset Pompe Disease

Case20: Female, 3 years onset, 4 years diagnosis

CaseAddInfo: Late-Onset Pompe Disease

Variant: NM_000152.4:c.380G>A (p.Cys127Tyr)

CAID: CA401360975 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.3%3Ac.380G%3EA

gnomAD: Not in gnomAD

VariantAddInfo: This variant was declared as novel and found in a patient, but no further information was given.

Variant: NM_000152.4:c.878G>T (p.Gly293Val)

CAID: CA401363883 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.3%3Ac.878G%3ET

gnomAD: Not in gnomAD

VariantAddInfo: This variant was declared as novel and found in a patient, but no further information was given.

Variant: NM_000152.4:c.1447G>T (p.Gly483Trp)

CAID: CA401366801 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.3%3Ac.1447G%3ET

gnomAD: Not in gnomAD

VariantAddInfo: This variant was declared as novel and found in a patient, but no further information was given.

Case3: Male, 1 year report

CasePresentingHPOs: HP:0002910, HP:0002058 (Elevated liver enzymes, Myopathic facies)

HPOsFreeText: Nonspecific hyperCKemia, 847 CK (U/L), 0 GAA activity (µmol/L/h)

CaseNotHPOs: HP:0001627, HP:0002093 (Abnormality of the heart, Respiratory insufficiency)

Case2: Male, 2 years report

CasePresentingHPOs: HP:0002910, HP:0002058 (Elevated liver enzymes, Myopathic facies)

HPOsFreeText: Nonspecific hyperCKemia, 1710 CK (U/L), 0.1 GAA activity (µmol/L/h)

CaseNotHPOs: HP:0003457, HP:0001627, HP:0002093 (EMG abnormality, Abnormality of the heart, Respiratory insufficiency)

Case1: Female, 12 years report, 3 years onset, 12 years diagnosis

CasePresentingHPOs: HP:0003325, HP:0002093, HP:0002650 (Limb-girdle muscle weakness, Respiratory insufficiency, Scoliosis)

HPOsFreeText: 730 CK (U/L), Normal Heart, 0 GAA activity (µmol/L/h), Showed respiratory involvement and required nocturnal non-invasive ventilation, An ambulant patient with 284 m six minute walk distance at the time of diagnosis

CaseNotHPOs: HP:0003457, HP:0001627 (EMG abnormality, Abnormality of the heart)

NotHPOsFreeText: Muscle weakness confined to limb-girdle muscles

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.

PatientF3P1: Female, 3 months diagnosis, Multiracial (maternal European and Native American and paternal Czechoslovakian, German, and Australian)

CasePresentingHPOs: HP:0004755, HP:0001290 (Supraventricular tachycardia, Generalized hypotonia)

CaseAddInfo: Proband

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

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

Case10HPOsFreeText: 20 mg/kg GAA treatment, GAA activity at 0.2 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.1548G>A (p.Trp516Ter)

ClinVar: 189025 https://www.ncbi.nlm.nih.gov/clinvar/variation/189025/

gnomAD: European (Non-Finnish) 1.552e-5, Overall 7.079e-6 https://gnomad.broadinstitute.org/variant/17-78084636-G-A

CaseAddInfo: Patient is compound heterozygous for this variant

Case1117: Male, 35 years onset, Welsh/English, Caucasian

CasePresentingHPOs: HP:0003560, HP:0005110 (Muscular dystrophy, Atrial fibrillation)

HPOsFreeText: 1,000 –2000's CK level, Immunohistochemistry: dystrophin, sarcoglycans, merosin

CaseNotHPOs: HP:0009051, HP:0002540 (Increased muscle glycogen content, Non-ambulatory)

Case3: Male, 35 years report, 5 years onset, Algeria, African

CasePresentingHPOs: HP:0003323, HP:0003749, HP:0002355, HP:0007340, HP:0008956, HP:0003484, HP:0003236, HP:0003198 (Progressive muscle weakness, Pelvic girdle muscle weakness, Difficulty walking, Lower limb muscle weakness, Proximal lower limb amyotrophy, Upper limb muscle weakness, Increased serum CK, Myopathy)

HPOsFreeText: At grade 3 of Vignos and Walton scales, CK rate was 5 times the normal value and AST and ALT were normal, EMG was compatible with a myopathic disorder, GAA activity measured in leukocytes was significantly decreased

CaseNotHPOs: HP:0003115, HP:0003116, HP:0001270, HP:0001290, HP:0002240, HP:0001640, HP:0005952, HP:0002540 (Abnormal ECG, Abnormal echocardiography, Motor delay, Generalized hypotonia, Hepatomegaly, Cardiomegaly, Decreased pulmonary function, Non-ambulatory)

Patient15: Male, 21 years report, 2 years onset

CasePresentingHPOs: N/A

HPOsFreeText: GAA activity 4.7% from a dried blood spot

CaseNotHPOs: HP:0002098, HP:0001324, HP:0001640, HP:0002240 (Respiratory distress, Muscle weakness, Cardiomegaly, Hepatomegaly)

NotHPOsFreeText: No wheelchair needed, Respiratory Assistance not needed

CaseAddInfo: LOPD

Patient30: Female, 1 year onset

CasePresentingHPOs: HP:0001324, HP:0001263 (Muscle weakness, Developmental delay)

HPOsFreeText: GAA activity 3% from leukocyte

CaseNotHPOs: HP:0002098, HP:0002240, HP:0001640 (Respiratory distress, Hepatomegaly, Cardiomegaly)

NotHPOsFreeText: No wheelchair needed, Respiratory Assistance not needed

CaseAddInfo: LOPD

Patient2: Female, 10 years report, 4 months onset

CasePresentingHPOs: HP:0001640, HP:0002098, HP:0002240 (Cardiomegaly, Respiratory distress, Hepatomegaly)

HPOsFreeText: GAA activity 4.6% from leukocyte, Respiratory Assistance needed

CaseNotHPOs: HP:0001324 (Muscle weakness)

NotHPOsFreeText: No wheelchair needed

CaseAddInfo: IOPD

Patient36: Male, 3 year onset

CasePresentingHPOs: HP:0001324, HP:0002098, HP:0003236 (Muscle weakness, Respiratory distress, Increased serum CK)

HPOsFreeText: GAA activity 5.7% from leukocyte, Wheelchair needed, Respiratory Assistance needed

CaseNotHPOs: HP:0001640, HP:0002240 (Cardiomegaly, Hepatomegaly)

NotHPOsFreeText: N/A

CaseAddInfo: LOPD550825

Patient19: Male, 21 years report, 14 year onset

CasePresentingHPOs: HP:0001324, HP:0002098 (Muscle weakness, Respiratory distress)

HPOsFreeText: GAA activity 9.3% from leukocyte, Respiratory Assistance needed

CaseNotHPOs: HP:0001640, HP:0002240 (Cardiomegaly, Hepatomegaly)

NotHPOsFreeText: Wheelchair not needed

CaseAddInfo: LOPD

Patient26: Male, 14 years report, 12 years onset

CasePresentingHPOs: HP:0001324 (Muscle weakness)

HPOsFreeText: GAA activity 5.1% from leukocyte

CaseNotHPOs: HP:0002098, HP:0002240, HP:0001640 (Respiratory distress, Hepatomegaly, Cardiomegaly)

NotHPOsFreeText: No wheelchair needed, Respiratory Assistance not needed

CaseAddInfo: LOPD

Patient25: Male, 15 years report, 2 years onset

CasePresentingHPOs: HP:0002527 (Falls)

HPOsFreeText: GAA activity 5.6% from leukocyte

CaseNotHPOs: HP:0002098, HP:0001324, HP:0001640, HP:0002240 (Respiratory distress, Muscle weakness, Cardiomegaly, Hepatomegaly)

NotHPOsFreeText: No wheelchair needed, Respiratory Assistance not needed

CaseAddInfo: LOPD

Patient14: Male, 59 years report, 40 year onset

CasePresentingHPOs: HP:0001324, HP:0002098 (Muscle weakness, Respiratory distress)

HPOsFreeText: GAA activity 6.9% from dried blood spot, Respiratory Assistance needed

CaseNotHPOs: HP:0001640, HP:0002240 (Cardiomegaly, Hepatomegaly)

NotHPOsFreeText: Wheelchair not needed

CaseAddInfo: LOPD

Case1: Male, French-Canadian, 18 years onset, 54 years diagnosis and report

CasePresentingHPOs: HP:0008994, HP:0000822, HP:0003119, HP:0004398, HP:0007185, HP:0009109, HP:0002094, HP:0012764, HP:0002098 (Proximal muscle weakness in lower limbs, High blood pressure, dyslipidemia, Peptic ulcer, Loss of consciousness, Denervation of the diaphragm, Dyspnea, Orthopnea, Shortness of breath)

HPOsFreeText: Dependent on continuous positive airway pressure or bilevel positive airway pressure when he is lying flat or sleeping because of previous intubation and tracheostomy, GAA activity measured from dried blood spot was 0.87 pmol/h/punch (Normal 4.96 - 27.3)

CaseAddInfo: Late Onset Pompe Disease, The patient’s mother had six miscarriages and died at age 75 of lung cancer and his father died of cardiac problems in his early sixties, It appears that no other family members, including his parents and two siblings, were affected, patient had a previous appendectomy, He has no allergies, stopped smoking in 2002, and denied any alcohol or drug use

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

Case18: Female, 50 years onset, 53 years diagnosis, Italy

HPOsFreeText: See Group Phenotypes, ERT started at 56, GAA Activity at ~6 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.1465G>A (p.Asp489Asn)

ClinVar: 92465 https://www.ncbi.nlm.nih.gov/clinvar/variation/92465/

gnomAD: European (Finnish) 4.621e-5, Overall 1.195e-5 http://gnomad.broadinstitute.org/variant/17-78084553-G-A

CaseAddInfo: Late Onset Pompe Disease

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

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

Patient7: 71yo

CasePresentingHPOs: HP:0003325, HP:0002093, HP:0002315, HP:0004887, HP:0000822, HP:0003141, HP:0002870, HP:0020038

HPOsFreeText: morning headache, GAA = 7%, BMI = 28.3, temporo-insular lacunes

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 18yr 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_000152.3:c.2530_2541del

CAID: CA658795292, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA658795292

gnomAD: n/a

Patient4: 19yo

CasePresentingHPOs:

HPOsFreeText: hyperCKemia, GAA = 24%, BMI = 26.1, normal CTA and CT

CaseNotHPOs:

NotHPOsFreeText: No cardiovascular risk

CaseAddInfo: 12yr disease duration

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.1771C>T (p.Arg591Trp)

ClinVar: 551782, https://www.ncbi.nlm.nih.gov/clinvar/variation/551782/

gnomAD: 8.662e-06, http://exac.broadinstitute.org/variant/17-78086393-C-T

Patient5: 36yo

CasePresentingHPOs: HP:0003325, HP:0002093, HP:0001513, HP:0002637

HPOsFreeText: GAA = 4.6%, BMI = 35.1, normal CTA, right temporal pole ischaemia

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo: 4yr 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_000152.3:c.2530_2541del

CAID: CA658795292, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA658795292

gnomAD: n/a

Patient7: Male

CasePresentingHPOs: HP:0002194

HPOsFreeText: ERT dosage = 20 mg/kg/2 w, CRIM positive

CaseNotHPOs: HP:0004887

NotHPOsFreeText: no reversal of HCM

CaseAddInfo: Symptom onset and diagnosis at 3mo, ERT at 4mo, ERT lasted for 24mo, died at 28mo

CasePMIDs: 22644586, 14695532

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.655G>A (p.Gly219Arg)

ClinVar: 189065, https://www.ncbi.nlm.nih.gov/clinvar/variation/189065/

gnomAD: 1.666e-05, http://exac.broadinstitute.org/variant/17-78079656-G-A

Patient6: Female

CasePresentingHPOs: HP:0002194, HP:0001522

HPOsFreeText: ERT dosage = 20 mg/kg/2 w, CRIM negative

CaseNotHPOs: HP:0004887

NotHPOsFreeText: No reversal of HCM

CaseAddInfo: Symptom onset at 1mo, diagnosis and ERT at 4mo, ERT lasted for 4mo, died at 11mo

CasePMIDs: 22252923, 27629047

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.3:c.1657C>T

CAID: CA401368835, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.3%3Ac.1657C%3ET

gnomAD: n/a

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

Patient11: Female

CasePresentingHPOs: HP:0004887, HP:0002100, HP:0006597, HP:0200136, HP:0011471

HPOsFreeText: ERT dosage = 40mg/kg/w, HCM reversal, CRIM positive, able to run, diaphragmatic paralysis required plication at 3yo

CaseNotHPOs: HP:0009046

NotHPOsFreeText:

CaseAddInfo: Symptom onset at 2mo, diagnosis at 4mo, ERT at 5mo, ERT lasted for 67mo, ventilation required at 62mo, currently 6yo

CasePMIDs: 14695532, 14972326

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.1064T>C (p.Leu355Pro)

ClinVar: 284093, https://www.ncbi.nlm.nih.gov/clinvar/variation/284093/

gnomAD: 8.304e-06, http://exac.broadinstitute.org/variant/17-78082197-T-C

Case#: Subject number 4, female, 11 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001638 (cardiomyopathy), HP:0002153 (hyperkalemia), HP:0001324 (muscle weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.16 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1831G>A (p.Gly611Ser)

Variant 2 ClinVarID: 935199

Variant 2 CAid: CA401369553

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 11, male, 51 years (report)

DiseaseAssertion: Pompe disease

FamilyInfo: No known family member with PD

CasePresentingHPOs: HP:0001324 (muscle weakness), HP:0003326 (Myalgia), HP:0002015 (dysphagia), HP:0002153 (hyperkalemia)

CaseHPOFreeText:

CaseNotHPOs: HP:0003546 (Exercise intolerance), HP:0001252 (Hypotonia), HP:0001638 (cardiomyopathy), HP:0002098 (respiratory distress), HP:0002094 (dyspnoea)

CaseNotHPOFreeText: no biopsy, not asymptomatic

CasePreviousTesting: "Enzymatic activity was detected by fluorometric techniques" "The GAA sequence was performed in all patients whose enzyme activity measured in DBS and lymphocytes was decreased."

glucosidase activity: GAA activity was 0.21 mol/Lh in dried blood spots (normal range >0.75).

Variant 1: NM_000152.5(GAA):c.-32-13T>C

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2104C>T (p.Arg702Cys)

Variant 2 ClinVarID: 189040

Variant 2 CAid: CA274304

Zygosity: Compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

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

Case#: Subject number 6(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 176 U/L (28-300 U/L is normal), AST: 61 U/L (24-72 U/L is normal), ALT: 39 U/L (17-63 U/L is normal), Hex4: 5.9 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 1.32 micromole/L/h and GAA activity #2 (NBS) 0.88 in dried blood spots (>2.10 micromole/L/h is normal). 0.7 in confirmatory testing (>6.7 is normal).

Variant 1: NM_000152.5(GAA):c.-32-13T>G

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.-32-13T>G

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 2(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 72 U/L (28-300 U/L is normal), AST: 21 U/L (24-72 U/L is normal), ALT: 23 U/L (17-63 U/L is normal), Hex4: 4.2 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal)

glucosidase activity: GAA activity #1 was 1.86 micromole/L/h and GAA activity #2 (NBS) 1.44 in dried blood spots (>2.10 micromole/L/h is normal). 5.3 in confirmatory testing (>6.7 is normal).

Variant 1: NM_000152.5(GAA):c.2238G>C

Variant 1 ClinVarID: 265160

Variant 1 CAid: CA8815665

Variant 2: NM_000152.5(GAA):c.1552-3C>G

Variant 2 ClinVarID: 419722

Variant 2 CAid: CA8815383

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 17(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: CK testing: 275 U/L (60-305 U/L is normal), AST: 150 U/L (22-71 U/L is normal), ALT: 42 U/L (7-50 U/L is normal), Hex4: 5.2 mmol/mol Creatinine (≤20 mmol/mol Creatinine is normal), BNP 44.5 pg/mL (0.0–100.0 pg/mL is normal)

glucosidase activity: GAA activity #1 was 1.04 micromole/L/h and GAA activity #2 (NBS) 0.77 in dried blood spots (>2.10 micromole/L/h is normal). 1.80 in confirmatory testing (>3.88 is normal).

Variant 1: NM_000152.5(GAA):c.-32-13T>G

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.-32-13T>G

Variant 2 ClinVarID: 4027

Variant 2 CAid: CA116606

Zygosity: homozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

PMID: 33202836

Gene: GAA

Disease: Pompe disease

Inheritance: Autosomal recessive

Case#: Subject number 29(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

glucosidase activity: GAA activity #2 (NBS) 0.48 in dried blood spots (>2.10 micromole/L/h is normal).

Variant 1: NM_000152.5(GAA):c.-32-13T>G

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.1547G>A

Variant 2 ClinVarID: 983721

Variant 2 CAid: CA401367155

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case#: Subject number 28(L)

DiseaseAssertion: Late Onset Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: N/A

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: N/A

glucosidase activity: GAA activity #2 (NBS) 1.06 in dried blood spots (>2.10 micromole/L/h is normal).

Variant 1: NM_000152.5(GAA):c.-32-13T>G

Variant 1 ClinVarID: 4027

Variant 1 CAid: CA116606

Variant 2: NM_000152.5(GAA):c.2238G>C

Variant 2 ClinVarID: 265160

Variant 2 CAid: CA8815665

Variant 3: NM_000152.5(GAA):c.2065G>A

Variant 3 ClinVarID: 4030

Variant 3 CAid: CA116612

Zygosity: compound heterozygous

ParentalGenotype: N/A

PreviouslyPublished: N/A

Case84

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.743T>C (p.Leu248Pro)

CAID: CA401363263 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.743T%3EC

gnomAD: European (Non-Finnish) 1.551e-5, Overall 7.079e-6 http://gnomad.broadinstitute.org/variant/17-78081406-T-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

Case59

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.1441T>C (p.Trp481Arg)

ClinVar: 189007 https://www.ncbi.nlm.nih.gov/clinvar/variation/189007/

gnomAD: African 8.031e-5, Overall 2.126e-5 http://gnomad.broadinstitute.org/variant/17-78084529-T-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

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

Case8

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.1754+1G>A

ClinVar: 286458 https://www.ncbi.nlm.nih.gov/clinvar/variation/286458/

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.722_723delTT (p.Phe241Cysfs*88)

CAID: CA658795235 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.722_723delTT

gnomAD: Not in gnomAD

CaseAddInfo: Infantile Onset Pompe Disease

Case90

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.925G>A (p.Gly309Arg)

ClinVar: 188797 https://www.ncbi.nlm.nih.gov/clinvar/variation/188797/

gnomAD: Ashkenazi Jewish 1.010e-4, Overall 2.860e-5 http://gnomad.broadinstitute.org/variant/17-78081665-G-A

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, 1 other patient has the same genotype

Case69

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.2238G>A (p.Trp746*)

ClinVar: 370904 https://www.ncbi.nlm.nih.gov/clinvar/variation/370904/

gnomAD: African 4.011e-5, Overall 1.063e-5 http://gnomad.broadinstitute.org/variant/17-78090815-G-A

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, 1 other patient has the same genotype

Case55

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.953T>C (p.Met318Thr)

ClinVar: 4021 https://www.ncbi.nlm.nih.gov/clinvar/variation/4021/

gnomAD: African 8.608e-5, Overall 4.485e-5 http://gnomad.broadinstitute.org/variant/17-78081693-T-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: Juvenile Late Onset Pompe Disease

Case35

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.2238G>A (p.Trp746*)

ClinVar: 370904 https://www.ncbi.nlm.nih.gov/clinvar/variation/370904/

gnomAD: African 4.011e-5, Overall 1.063e-5 http://gnomad.broadinstitute.org/variant/17-78090815-G-A

Variant2: NM_000152.4:c.1843G>A (p.Gly615Arg)

ClinVar: 188786 https://www.ncbi.nlm.nih.gov/clinvar/variation/188786/

gnomAD: East Asian 2.223e-4, Overall 1.640e-5 http://gnomad.broadinstitute.org/variant/17-78086465-G-A

CaseAddInfo: Infantile Onset Pompe Disease

Case38

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.1912G>T (p.Gly638Trp)

CAID: 280954 https://www.ncbi.nlm.nih.gov/clinvar/variation/280954/

gnomAD: African 6.752e-5, Overall 1.239e-5 http://gnomad.broadinstitute.org/variant/17-78086698-G-T

CaseAddInfo: Infantile Onset Pompe Disease

Case29

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.1293_1312del (p.Gln433Aspfs*66)

CAID: CA658795249 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1293_1312del

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.1716C>G (p.His572Gln)

CAID: CA401369055 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.1716C%3EG

gnomAD: Not in gnomAD

CaseAddInfo: Infantile Onset Pompe Disease

Case24

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.2560C>T (p.Arg854*)

ClinVar: 4034 https://www.ncbi.nlm.nih.gov/clinvar/variation/4034/

gnomAD: African 1.891e-3, Overall 2.090e-4 http://gnomad.broadinstitute.org/variant/17-78092070-C-T

Variant2: NM_000152.4:c.2459_2461delCTG (p.Ala820del)

ClinVar: 456404 https://www.ncbi.nlm.nih.gov/clinvar/variation/456404/

gnomAD: European (Non-Finnish) 6.492e-5, Overall 3.190e-5 http://gnomad.broadinstitute.org/variant/17-78091524-GGCT-G

CaseAddInfo: Infantile Onset Pompe Disease

CaseOPOPD-50: Male, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 0.68 umol/hr/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.1634C>T (p.Pro545Leu)

ClinVar: 4032 https://www.ncbi.nlm.nih.gov/clinvar/variation/4032/

gnomAD: European (Finnish) 1.199e-4, Overall 1.774e-5 http://gnomad.broadinstitute.org/variant/17-78084822-C-T

Variant2: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

CaseAddInfo: One Pompe Mutation allele and One Pseudodeficency Mutation allele

CaseOPTPD-5: Female, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 1.27 umol/hr/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

Variant2: NM_000152.4:c.1222A>G (p.Met408Val)

ClinVar: 371235 https://www.ncbi.nlm.nih.gov/clinvar/variation/371235/

gnomAD: European (Non-Finnish) 1.790e-5, Overall 8.058e-6 http://gnomad.broadinstitute.org/variant/17-78082523-A-G

CaseAddInfo: One Pompe Mutation allele and Two Pseudodeficency Mutation alleles, Nomenclature indicates patient is homozygous for Variant 1 and Variant 2 is in cis with one copy

CaseOPOPD-40: Female, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 0.99 umol/hr/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.872T>C (p.Leu291Pro)

CAID: CA401363854 https://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/allele?hgvs=NM_000152.4%3Ac.872T%3EC

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

CaseAddInfo: One Pompe Mutation allele and One Pseudodeficency Mutation allele, 2 others have the same genotypes

CaseLP2-12: Male, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 0.43 umol/hr/L, Serum CK at 29 U/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.1935C>A (p.Asp645Glu)

ClinVar: 4029 https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: East Asian 1.729e-3, Overall 1.240e-4 http://gnomad.broadinstitute.org/variant/17-78086721-C-A

Variant2: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

Variant3: NM_000152.4:c.2482-5T>C

ClinVar: 558320 https://www.ncbi.nlm.nih.gov/clinvar/variation/558320/

gnomAD: Not in gnomAD

CaseAddInfo: Late Onset Pompe Disease, Nomenclature indicates Variants 1 and 2 are in cis one one allele and Variants 2 and 3 are in cis on the other

CaseOPOPD-52: Male, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 1.05 umol/hr/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

Variant2: NM_000152.4:c.1843G>A (p.Gly615Arg)

ClinVar: 188786 https://www.ncbi.nlm.nih.gov/clinvar/variation/188786/

gnomAD: East Asian 2.223e-4, Overall 1.640e-5 http://gnomad.broadinstitute.org/variant/17-78086465-G-A

CaseAddInfo: One Pompe Mutation allele and One Pseudodeficency Mutation allele, 1 other patient has the same genotype

CaseOPOPD-45: Female, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 1.46 umol/hr/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.1411_1414delGAGA (p.Glu471Profs)

ClinVar: 188874 https://www.ncbi.nlm.nih.gov/clinvar/variation/188874/

gnomAD: East Asian 2.513e-4, Overall 1.781e-5 http://gnomad.broadinstitute.org/variant/17-78083827-CGAGA-C

Variant2: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

CaseAddInfo: One Pompe Mutation allele and One Pseudodeficency Mutation allele, 1 other has the same genotype

CaseOPOPD-4: Female, Taiwan, Birth diagnosis

HPOsFreeText: GAA (MS/MS) enzyme activity at 1.16 umol/hr/L

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.460_465del (p.Arg154_Thr155del)

ClinVar: 551306 https://www.ncbi.nlm.nih.gov/clinvar/variation/551306/

gnomAD: Not in gnomAD

Variant2: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

CaseAddInfo: One Pompe Mutation and One Pseudodeficency Mutation

CaseLP-5: Male, Taiwan, Birth diagnosis

HPOsFreeText: 4MU enzyme activity at 1.08, MS/MS ennzyme activity at 0.46

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.752C>T (p.Ser251Leu)

ClinVar: 325781 https://www.ncbi.nlm.nih.gov/clinvar/variation/325781/

gnomAD: East Asian 2.760e-3, Overall 3.540e-4 http://gnomad.broadinstitute.org/variant/17-78081415-C-T

Variant2: NM_000152.4:c.761C>T (p.Ser254Leu)

ClinVar: 325782 https://www.ncbi.nlm.nih.gov/clinvar/variation/325782/

gnomAD: East Asian 2.759e-3, Overall 1.947e-4 http://gnomad.broadinstitute.org/variant/17-78081424-C-T

Variant3: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

Variant4: NM_000152.4:c.1935C>A (p.Asp645Glu)

ClinVar: 4029 https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: East Asian 1.729e-3, Overall 1.240e-4 http://gnomad.broadinstitute.org/variant/17-78086721-C-A

CaseAddInfo: Suspected Late Onset Pompe Disease, Nomenclature indicates Variants 1 and 2 are in cis and Variants 3 and 4 are also in cis

CasePDC-3: Female, Taiwan, Birth diagnosis

HPOsFreeText: 4MU enzyme activity at 1.26, MS/MS ennzyme activity at 1.21

GenotypingMethod: GAA Gene Sequencing and PCR Amplification

Variant1: NM_000152.4:c.752C>T (p.Ser251Leu)

ClinVar: 325781 https://www.ncbi.nlm.nih.gov/clinvar/variation/325781/

gnomAD: East Asian 2.760e-3, Overall 3.540e-4 http://gnomad.broadinstitute.org/variant/17-78081415-C-T

Variant2: NM_000152.4:c.761C>T (p.Ser254Leu)

ClinVar: 325782 https://www.ncbi.nlm.nih.gov/clinvar/variation/325782/

gnomAD: East Asian 2.759e-3, Overall 1.947e-4 http://gnomad.broadinstitute.org/variant/17-78081424-C-T

Variant3: NM_000152.4:c.1726G>A (p.Gly576Ser)

ClinVar: 92467 https://www.ncbi.nlm.nih.gov/clinvar/variation/92467/

gnomAD: East Asian 0.1427, Overall 0.01700 http://gnomad.broadinstitute.org/variant/17-78085871-G-A

CaseAddInfo: Patient is either a carrier or has a pseudodeficency allele, Nomenclature indicates that Variants 1 and 2 are in cis, PDC-4 and 5 have the exact same allele combination

Case#: Patient 7, Gender N/A, Onset 3-4 months. Death around 1-2 years, Southeast Asian

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: P:0001639. HP:0005165, HP:0001270, HP:0002240

(Dyspnea, Shortened PR interval, Motor delay, Hepatomegaly

CaseHPOFreeText: BVH, Severe MR, SDD, CK 550u/l, EF

CaseNotHPOs:

CaseNotHPOFreeText:

CasePreviousTesting: Creatine Kinase enzyme 550u/l, Ejection fraction 30%, GAA enzyme activity in leukocytes was 0.05% of normal control value.

PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions

Variant 1: NM_000152.5(GAA):c.1411_1414del (p.Glu471fs)

ClinVar: 188874

CAID: CA274067

gnomAD: Highest population MAF = 0.0002513 in East Asian

Variant 2: NM_000152.5(GAA):c.1933G>C (p.Asp645His)

ClinVar: 189013

CAID: CA274256

gnomAD: Highest population MAF = 0.00005534 (East Asian)

ParentalGenotype: Father was the carrier of variant 1 NM_000152.5(GAA):c.1411_1414del (p.Glu471fs)

mother was carrier of variant 2 NM_000152.5(GAA):c.1933G>C (p.Asp645His)

PreviouslyPublished: N/A

Case#: Patient 12, Gender N/A, Onset at 3-4 months old, Southeast Asian

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001252, HP:0002090, HP:0002878, HP:0005165

(Hypotonia, Pneumonia, Respiratory failure, Shortened PR interval)

CaseHPOFreeText: Failed endotracheal extubation, BVH, mild sub-aortic obstruction, SDD, Ejection fraction 13%, creatine kinase levels 966 u/l

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: GAA enzyme activity in leukocytes was 0.10% of normal control value.

PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions

Variant 1: c.1327-2A>G

ClinVar: N/A

CAID: CA401366177

gnomAD: Highest population MAF = 0.0002297 (African)

Variant 2: c.1437G>C (p.Lys479Asn)

ClinVar: N/A

CAID: CA401366671

gnomAD: N/A

ParentalGenotype: Mother was the carrier of variant 1 c.1327-2A>G

Father was the carrier of variant 2 c.1437G>C (p.Lys479Asn)

PreviouslyPublished:

Case#: Patient 1, gender N/A, Age of onset was 7-8 months (died at 3 years of age), Southeast Asian

DiseaseAssertion: Pompe Disease

FamilyInfo:

CasePresentingHPOs: HP:0001252, HP:0001270, HP:0001638, HP:0005165 (Muscular Hypotonia, Motor delay, Cardiomyopathy, Shortened PR interval)

CaseHPOFreeText: N/A

CaseNotHPOs: N/A

CaseNotHPOFreeText: N/A

CasePreviousTesting: GAA activity in leukocytes was 0% of the normal control value.

PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions

Variant1: NM_000152.5(GAA):c.876C>G (p.Tyr292Ter)

ClinVar: 637958

CAID: CA401363871

gnomAD: N/A

Variant2: NM_000152.5:c.1003G>A (p.Gly335Arg)

ClinVar: 972790

CAID: CA501005

gnomAD: Highest population MAF = 0.00003266 (South Asian).

ParentalGenotype: Patient inherited variant 1 (NM_000152.5(GAA):c.876C>G (p.Tyr292Ter) from father.

Variant 2 (c.1003G>A (p.Gly335Arg)) was inherited from mother PreviouslyPublished:N/A

Case#: Patient 2, Gender N/A, 1-2 months old at onset, Southeast Asian

DiseaseAssertion: Pompe disease

FamilyInfo: Patient has two previously deceased siblings with cardiomyopathy

CasePresentingHPOs: HP:0002789, HP:0002240, HP:0005165, HP:0001639 (Tachypnea, Hepatomegaly, Shortened PR interval, Hypertrophic cardiomyopathy)

CaseHPOFreeText: BVH, EF 30%

CaseNotHPOs: N/A

CaseNotHPOFreeText:N/A

CasePreviousTesting: GAA activity in leukocytes was 0% of the normal control value

PCR of all exons was performed and subsequently subjected to capillary Sanger sequencing in both directions

Variant1: NM_000152.5(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029

CAID: CA116610

gnomAD: Highes population MAF = 0.001729 (East Asian)

Variant2: NM_000152.5(GAA):c.1933G>C (p.Asp645His)

ClinVar:<br /> 189013

CAID: CA274256

gnomAD: Highest population MAF = 0.00005534 (East Asian)

ParentalGenotype: Father was carrier of variant 1 c.1935C>A ( p.Asp645Glu

Mother was carrier of the Variant 2 c.1933G>C (p.Asp645His

PreviouslyPublished:

PMID: 31510962

Gene:GAA

Case#: Subject number 7, male, 62 years (diagnosis), 66 years (baseline visit), 67 years (ERT), 67 years (ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 2, female, 20 years (diagnosis), 48 years (baseline visit), 39 years (ERT), 34 years (ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 30, male, 12 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)

CaseHPOFreeText:

CaseNotHPOs: HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress), HP:0001324 (Muscle Weakness)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 5, female, 20 years (diagnosis), 45 years (baseline visit), 42 years (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 4, female, 56 years (diagnosis), 63 years (baseline visit), 59 years (ERT)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness)

CaseHPOFreeText:

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 25, male, 41 years (diagnosis), 46 years (baseline visit), 43 years (ERT), 43 (age at ventilation)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseHPOFreeText: mechanical ventilation at Baseline Visit, mechanical ventilation at last visit

CaseNotHPOs: HP:0003236 (Elevated circulating creatine kinase concentration), HP:0002870 (obstructive sleep apnea)

CaseNotHPOFreeText:

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 36, male, 44 years (diagnosis), 49 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)

CaseHPOFreeText:

CaseNotHPOs: HP:0002098 (respiratory distress), HP:0002870 (obstructive sleep apnea), HP:0001324 (Muscle Weakness)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Subject number 3, female, 26 years (baseline visit)

DiseaseAssertion: Pompe disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0003236 (Elevated circulating creatine kinase concentration)

CaseHPOFreeText:

CaseNotHPOs: HP:0002870 (obstructive sleep apnea), HP:0001324 (Muscle Weakness), HP:0002098 (respiratory distress)

CaseNotHPOFreeText: no mechanical ventilation at Baseline Visit, no mechanical ventilation at last visit

CasePreviousTesting: "reduced enzymatic activity on fibroblasts, blood leukocytes or skeletal muscle and/or the presence of two known mutations in the GAA gene"

PreviouslyPublished: N/A

Case#: Patient 1, female, symptoms began at birth, began ERT at 2.4mo

DiseaseAssertion: Pompe Disease

FamilyInfo: N/A

CasePresentingHPOs: HP:0002789, HP:0001639, HP:0010628, HP:0000010 (tachypnea, hypertrophic cardiomyopathy, facial nerve palsy, persistent urinary tract infections)

CaseHPOFreeText: diagnosed IOPD, frequent airway infections, motor function significant decline

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.2481+102_2646+31del538

Variant 1 ClinVarID: 657307

Variant 1 CAid: CA65879529

Variant 2: NM_000152.5:c.2481+102_2646+31del538

Variant 2 ClinVarID: 657307

Variant 2 CAid: CA658795291

ParentalGenotype: Not provided

PMID: 31256280

Gene: GAA

Disease: Pompe Disease

Inheritance: Autosomal Recessive

Patient4: IOPD Group, 12 days old

CasePresentingHPOs:

HPOsFreeText: LDH = 432 U/L, CK = 458 U/L, ALT = 37 U/L, AST = 80 U/L, Mann-Whitney Test = 3

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant1: NM_000152.3:c.872T>C

CAID: CA401363854, http://reg.clinicalgenome.org/redmine/projects/registry/genboree_registry/by_caid?caid=CA401363854

gnomAD: n/a

Variant2: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: 0.0001240, https://gnomad.broadinstitute.org/variant/17-78086721-C-A

Patient2: IOPD Group, 10days old

CasePresentingHPOs:

HPOsFreeText: LDH = 516 U/L, CK = 385 U/L, ALT = 12 U/L, AST = 73 U/L, Mann-Whitney Test = 2

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: 0.0001240, https://gnomad.broadinstitute.org/variant/17-78086721-C-A

Patient8: IOPD Group, 12days old

CasePresentingHPOs:

HPOsFreeText: LDH = 418 U/L, CK = 483 U/L, ALT = 44 U/L, AST = 93 U/L, Mann-Whitney Test = 2

CaseNotHPOs:

NotHPOsFreeText:

CaseAddInfo:

CasePMIDs:

CasePreviousTesting: same as group

CaseGenotypingMethod: same as group

Variant: NM_000152.4(GAA):c.1935C>A (p.Asp645Glu)

ClinVar: 4029, https://www.ncbi.nlm.nih.gov/clinvar/variation/4029/

gnomAD: 0.0001240, https://gnomad.broadinstitute.org/variant/17-78086721-C-A