Fabry disease: enzyme replacement therapy

Fabry disease is a multisystem disorder associated with wide variability in clinical expression. Fabry disease is an X-linked lysosomal storage disorder caused by a deficiency of alpha-galactosidase A. The enzyme defect leads to the systemic accumulation of glycosphingolipids with alpha-galactosyl moieties consisting predominantly of globotriaosylceramide, galabiosylceramide and two additional glycosphingolipids. Four hemizygotes patients with a family history of Fabry disease and deficiency of the enzyme alpha-galactosidase A were selected. Each patient received purified alpha-galactosidase by intravenous infusion (0.2 mg/kg). The infusion was administered every 2 weeks, for 40 min, for a total of 12 months. Outcome measures include neurological manifestations (acroparaesthesia, hypohidrosis, vasomotion), kidney function, cardiac manifestations, angiokeratomas, and corneal dystrophy. alpha-Galactosidase A prepared from human fibroblast is safe and well tolerated. After 12 months of therapy the mean creatinine clearance increased, there was significant improvement in the acroparaesthesias and in the hypohidrosis. Physical stigmata, such as angiokeratomas in the skin, and characteristic benign corneal abnormalities remained stable. Enzyme replacement therapy would therefore represent a significant advance in treatment of patients with Fabry disease. Enzyme replacement therapy is safe and likely to improve the prognosis of Fabry disease.