Cardiac and motor improvement with enzyme replacement therapy in a patient with infantile-onset Pompe disease

Pompe disease (MIM #232300) is an autosomal recessive lysosomal storage disorder caused by mutation within the gene encoding the acid alpha-1,4-glucosidase (GAA) leading to a deficiency of GAA and accumulation of glycogen in muscle. Hypertrophic cardiomyopathy and muscular hypotonia are the cardinal features in the classic infantile-onset form of the disorder in which death typically occurs in the first years of life. Recombinant human acid alpha-glucosidase (rhGAA) derived from a chinese hamster ovary cell line is currently being evaluated as enzyme replacement (ERT) therapy in clinical trials. In this case report, we present the results of the cardiac, motor and cognitive evaluations before and one year after the initiation of ERT in a patient with infantile-onset Pompe disease. The infant presented with cyanosis, muscular hypotonia and retardation. At the age of 8 months he was diagnosed with a non-obstructive hypertrophic cardiomyopathy. Cardiac function was stabilised with beta-blockers. Muscle biopsy confirmed the diagnosis of Pompe disease. The patient was started on rhGAA 20mg/kg every 2 weeks at the age of 15 months. After 1 year of therapy, echocardiography demonstrated normalization of cardiac function and the patient no longer required cardiac medication. The diastolic intraventricular septum thickness decreased from 0,82cm to 0,48cm. The Alberta Infant Motor Scale Assessment showed an improvement of the total score from 19 to 39 (equivalent age of 8,4 months) at baseline and 1 year, respectively. The Pediatric Evaluation of Disability Inventory (PEDI) as well as the GSD II PEDI showed improvements in all tested subgroups of the patients skills. The patient achieved 3 new motor milestones after one year of treatment: the patient bears weight on his legs while standing with support, sits up without help and shows no head lag while pulled up to sitting position at the age of 27 month. Treatment of a patient with infantile-onset Pompe disease with rhGAA for one year led to improvement in both cardiac and motor function.