Research Paper: Fabry’s Disease
Fabry’s Disease, one of the lysosomal storage disorders belonging to the wide spectrum of inborn errors of metabolism, was first described in 1898 (Zarate & Hopkin, 2008). Till date, up to 60 lysosomal storage diseases have been defined, all of which manifest in different ways as a result of an accumulation of substrates due to the deficiency of one or more of the lysosomal enzymes (Linthorst, Hollak, Donker-Koopman, Strijland, & Aerts, 2004). Fabry’s Disease is an X-linked inherited disorder which has a wide variety of clinical manifestations resulting from the deficiency of the lysosomal enzyme α-galactosidase A (Zarate & Hopkin, 2008). Studies have revealed that deficiency of this enzyme can result from any of about 356different mutations.
The α -galactosidase A deficiency leads to impaired glycosphingolipid catabolism resulting in the accumulation of upstream substrate compounds such as globotriaosylceramide (Gb3) and galactosylceramide in various tissues throughout the body (Kosch, et al., 2004; Zarate & Hopkin, 2008). The progressive accumulation of these substrates is the main reason behind the myriad of ways in which this disease presents, with symptoms and prognosis worsening with increasing age. The main cells where the accumulation of glycosphingolipids occurs are the endothelial cells, accounting for the various vascular complications of Fabry’s Disease such as stroke, cardiomyopathy and renal failure (Linthorst, Hollak, Donker-Koopman, Strijland, & Aerts, 2004).