Fabry disease

Abstract

Fabry disease (FD) is an X-linked lysosomal disorder caused by the deficient activity of the enzyme alpha-galactosidase A, which leads to multisystemic storage of globotriaosylceramide in visceral tissues and vascular endothelium. FD manifests primarily in affected hemizygous men, with a wide range of clinical signs in heterozygous women. Acroparesthesias, angiokeratomas, pain crisis, and cornea verticillata are early manifestations of FD. With age, severe complications involving the kidneys, heart, and brain cause considerable morbidity and premature death. Although the clinical onset of FD occurs in childhood, diagnosis is often delayed or missed. In men, the diagnosis must be confirmed biochemically by demonstration of decreased levels of alpha-galactosidase A activity. In women, the disease is diagnosed by identification of a mutation in the alpha-galactosidase A gene. Until a few years ago, the existing treatment for FD was based on clinical manifestations, but the advent of enzyme replacement therapy should stimulate the identification of the signs and symptoms suggestive of this disorder to allow earlier diagnosis and treatment.