AUTOPHAGIC MYOPATHIES / MYOFIBRILLAR MYOPATHIES / DISTAL MYOPATHIES / POMPE DISEASE: P.05 Infantile onset Pompe disease: 10 years of experience in a pediatric reference centre for neuromuscular diseases

Abstract

Pompe disease is caused by mutations of the acid α-glucosidase gene (GAA) that result in reduced activity of the lysosomal enzyme GAA. Pompe disease can be divided into infantile-onset (IOPD) and late-onset (LOPD) type. Enzyme replacement therapy (ERT) has deeply modified the clinical history of Infantile Onset Pompe Disease (IOPD). This is a retrospective observational study of 4 patients with IOPD that have been followed up for 10 years. All the patients presented at the neonatal period severe hypotonia and hypertrophic myocardiopathy. CK levels were between 600-1200 IU/L. Residual GAA activity was less than 1% of the normal value. Cross-reactive immunological material (CRIM) positivity was found in 1 patient. In two patients, the CRIM test was not performed, but the predictions. Genetics test: The four patients presented a pathogenic variant in GAA gene. Evolution: Two patients died at 7 and 10 months; both patients showed IgG antibodies to rh-GAA with levels of, 12500 and 6800 respectively at early stages of disease and no positive response were. The time to start treatment ranged from 24 hours to 5 months. The other two patients (brothers) presented a follows: A 10 year old boy achieved ambulation at the age of 2 years. After a respiratory infection and femur fracture lost his gait and is currently in a wheelchair with an adequate strength of upper limbs. A 10 month old boy, can sit without support and does not require respiratory support. In both patients, we found a considerable reduction of the hypertrophic cardiomyopathy. In IOPD, the therapeutic response to ERT depends on multiple factors such as the age of onset, CRIM positive or negative testing results and the type of mutation. We need better understanding of response modifiers in CRIM+ patients other than antibody levels. Early onset treatment is a variable on which we can have an influence. The good responses observed in the initial phases of treatment do not continue long term.