Anderson-Fabry disease. Introduction

Abstract

Anderson-Fabry (or Fabry) disease was named after the two dermatologists who, independently, described it for the first time at the end of the 19th century. It is a metabolic lysosomal storage disorder which is due to the functional deficit of the enzyme alpha-galactosidase A (��-GAL A). The deficit alters the metabolism of some glycosphingolipids, especially globotriaosylceramide (Gb3) and lyso-Gb3 (the deacetylated form), causing their storage in lysosomes of various cell types but mainly those of the vascular endothelium. The storage is responsible for the systemic clinical manifestations of Anderson-Fabry disease and the renal, cardiac and cerebrovascular complications that may lead to a premature death between the fourth and fifth decades of life. Regarding its etiology, Fabry disease is an X-linked lysosomal enzymopathy caused by mutations in the GLA gene encoding ��-GAL A. To date, more than 900 mutations have been described in patients with the disease. Fabry disease is suspected on the basis of clinical and history-familial data, and is confirmed by biochemical and genetic assays including identification of specific genetic alterations and assessment of the ��-GAL A activity, which can be diminished or null. Also evaluation of substrates of the enzyme, Gb3 and lyso-Gb3, is used as a diagnostic tool.