Clinical features of and recent advances in therapy for Fabry disease.

Fabry disease is an X-linked recessive lysosomal storage disorder caused by a deficiency of alpha-galactosidase A. Intracellular accumulation of globotriaosylceramide, the glycolipid substrate of this enzyme, leads to severe painful neuropathy with progressive renal, cardiovascular, and cerebrovascular dysfunction and early death. Men are predominantly affected but many female carriers have similar clinical involvement, including increased risk of stroke. Physical stigmata, such as angiokeratomas in skin and mucous membranes and characteristic benign corneal abnormalities, facilitate identification of Fabry disease. The finding of a marked decreased activity of alpha-galactosidase A in white blood cells or cultured skin fibroblasts confirms the diagnosis. Treatment thus far has been symptomatic only. Etiology-based therapies are being developed that include enzyme replacement therapy, gene therapy, and substrate deprivation. Our recently completed double-blind, placebo-controlled trial of intravenous infusions of alpha-galactosidase A in patients with Fabry disease demonstrated the safety and efficacy of this treatment. JAMA. 2000;284:2771-2775.