Author Affiliations: Developmental Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md.
Grand Rounds at the Clinical Center of the National
Institutes of Health Section Editors: John I. Gallin, MD, the Clinical
Center of the National Institutes of Health, Bethesda, Md; David S. Cooper,
MD, Contributing Editor, JAMA.
Fabry disease is an X-linked recessive lysosomal storage disorder caused
by a deficiency of α-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 α-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 α-galactosidase A in patients with
Fabry disease demonstrated the safety and efficacy of this treatment.
Brady RO, Schiffmann R. Clinical Features of and Recent Advances in Therapy for Fabry Disease. JAMA. 2000;284(21):2771-2775. doi:10.1001/jama.284.21.2771