Enzyme-Replacement Therapy in Fabry Disease

Abstract

Fabry disease is a rare X-linked lysosomal storage disorder due to mutations in the GLA gene causing complete or partial deficiency of the lysosomal enzyme alpha-galactosidase A (a-Gal A). This enzyme deficiency results in tissue accumulation of trihexosylceramide causing the diseases’ systemic manifestations, including acroparesthesia, angiokeratomas, cardiac disease, cerebrovascular manifestations, and kidney disease. Kidney manifestations of Fabry disease can include proteinuria, renal tubular dysfunction, hypertension, and cystic formation. With the relatively recent introduction of enzyme-replacement therapy (ERT), this congenital disorder can now be treated providing these patients with much longer life expectancies and less severe systemic manifestations than before. When started in the appropriate population, ERT is generally continued until a reason for stopping therapy arises. Although ERT is expensive, it has drastically changed the clinical outcome of patients with Fabry disease, and timely initiation of ERT and regular assessments of disease progression by a multidisciplinary care team are critical for the long-term management of these patients.