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