Fabry Disease: A Rare Condition Emerging From the Darkness.

Abstract

Fabry (or Anderson–Fabry) disease—first described in 1898 by Johannes Fabry in Germany and William Anderson in England—is a lysosomal storage disease caused by mutations in the GLA gene located on the X chromosome (Xq22.1).1 These cause deficiency of the enzyme aGal A (alpha galactosidase A) and the accumulation of glycosphingolipids, particularly globotriaosylceramide, in different cell types. Over 800 individual missense or nonsense point mutations, splicing mutations, deletions, and insertions are reported, the majority of which render the aGal A enzyme nonfunctional.2 Some variants are associated with residual aGal A activity (typically 2%–20% of normal values) that results in attenuated forms of the disease. Although Fabry disease (FD) is an X–linked trait, women with GLA mutations can develop signs and symptoms of FD, which are usually milder than seen in affected men but cases of severe disease are well recognized, possibly as the result of skewed X chromosome inactivation.3 See Article by Adalsteinsdottir et al In this edition of the journal, Adalsteinsdottir et al4 describe the clinical phenotypes of 2 families—identified during genetic screening …