Phenotype variations in early onset Pompe disease: diagnosis and treatment results with Myozyme

Abstract

Pompe disease is a rare autosomal recessive lysosomal storage disease caused by deficiency of acid-a-glucosidase (GAA). This deficiency results in glycogen accumulation in the lysosomes, leading to lysosomal swelling, cellular damage and organ dysfunction. Patient age at the onset of Pompe disease symptoms and the rate of deterioration can vary considerably. In early onset patients (the classical infantile form) this glycogen accumulation leads to death usually before the age of 1 year. Some patients with early onset don't develop cardiomyopathy and their progression is slower (atypical infantile form). The late-onset form (juvenile and adult forms) have more slow and variable course. The gene is localized in 17q25. More than 200 different mutations have already been described. Diagnosis has been classically made by mean of muscular biopsy. Nowadays is more convenient the screening of GAA in dried blood sample followed by GAA assessment in lymphocytes or fibroblasts or by the genetic study of mutations. Besides non specific multiprofessional management, since 2006 there is a specific enzyme replacement therapy (ERT), Myozyme), which compensates for the missing enzyme by i.v. administration of recombinant produced enzyme. In classic Pompe disease the reported results improve significantly the survival, the motor development and the cardiac function. The sooner ERT starts, the better are the results. In late onset Pompe disease ERT has also demonstrated significant improvement in muscular function and quality of life.