Conclusions: This study indicates that the iPS and skeletal muscle cells generated in this study could also be a useful disease model for studies investigating the pathogenesis and treatment of SM in Pompe disease. The heterogeneous response of skeletal muscle to enzyme replacement therapy (ERT) causes variable disability, from hypotonia to respiratory failure, in patients with infantile onset Pompe disease (IOPD). Histomorphometrical analysis reflects the extent of glycogen clearance and muscle damage, and may have a prognostic value. Two patients with IOPD, who started ERT at 2 months of age, had quadriceps biopsy during gastrostomy for feeding problem. Patient 1 responded well to ERT until late infancy, with motor regression and dependency on non-invasive ventilation since 14 months of age. Muscle biopsy at 15 months showed muscle fibres with abundant glycogen and minimal residual myofibril. He succumbed at 22 months of age. Patient 2 was well in the first 3 years. She then developed recurrent aspiration pneumonia and had gastrostomy at 43 months of age. She had satisfactory cardiorespiratory status and could walk independently. Light microscopy revealed variable glycogen content in muscle fibres and patchy involvement. More extensive glycogen overload was observed in the ultrastructural study. She eventually required walking-aid and non-invasive ventilation by 4 years of age. Our findings support the correlation between histology and clinical state, but caution the risk of sampling errors. Further studies are needed to evaluate its prognostic value. Conflict of Interest declared. Background: Pompe disease (glycogenosis type II) is a lysosomal storage disorder due to deficiency of glucosidase enzyme activity which leads to accumulation of glycogen in the cardiac and skeletal muscle. In the newborn predominant clinical presentation is hypertrophic cardiomyopathy, hypotonus and macroglossia. Case report: Our patient presented on the II day of life on a routine clinical examination with splitting of the second heart sound without any other clinical signs or abnormal fetal heart ultrasound. Electrocardiogram (ECG) showed typical Pompe disease related abnormalities and the heart ultrasound severe cardiac hypertrophy. Reduced enzyme activity (0,027, range 2,31-27,38 mcmol/L/h) on the blood spot was assessed within 48 hours by Tandem MS, further investigations (enzyme activity in leucocytes and fibroblasts, mutation analysis) were subsequently performed. In the meantime ERT was started on the VIII day of life. Conclusions: In the newborn unspecific cardiac findings may be Pompe disease related. Earliest detection of the reduced glucosidase activity by Tandem MS is a reliable method which allows timely introduction of the only therapeutic approach, the enzyme replacement therapy and normalisation of cardiomyopathy. Mutation analysis in our patient revealed a condition of compound heterozygousity of two novel splicing mutations: c.955+1 G>A and c.1438-2A>G.