Narrative Review: Fabry Disease

20 March 2007 | Volume 146 Issue 6 | Pages 425-433

Fabry disease is an X-linked, hereditary, lysosomal storage disease caused by deficiency of the enzyme -galactosidase A, which results in the accumulation of the neutral glycosphingolipid globotriaosylceramide (Gb3) in the walls of small blood vessels, nerves, dorsal root ganglia, renal glomerular and tubular epithelial cells, and cardiomyocytes. It is a complex, multisystem disorder that is characterized clinically by chronic pain and acroparesthesia, gastrointestinal disturbances, characteristic skin lesions (angiokeratomata), progressive renal impairment, cardiomyopathy, and stroke. Enzyme replacement therapy (ERT) with intravenous infusions of recombinant human -galactosidase A consistently decreases Gb3 levels in plasma and clears lysosomal inclusions from vascular endothelial cells. The effects of ERT on other tissues are not as obvious, suggesting that treatment must be initiated early in the course of the disease to be optimally effective or that some complications of the disease are not responsive to enzymes delivered intravenously.

Author and Article Information

From the Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada; and Centre Hospitalier Universitaire de Sherbrooke, Hôpital Fleurimont, Sherbrooke, Québec, Canada.

Potential Financial Conflicts of Interest: Honoraria: Genzyme Corp., Genzyme Canada, Transkaryotic Therapies Inc., Shire HGT; Grants received: Genzyme Corp., Genzyme Canada, Transkaryotic Therapies Inc., Shire HGT.

Requests for Single Reprints: Joe T.R. Clarke, MD, PhD, Division of Clinical & Metabolic Genetics, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada; e-mail, jtrc{at}sickkids.ca.