The reduced activity of the lysosomal enzyme, α-galactosidase A (α-Gal A) leads to classic early manifestations and vascular disease of the heart, kidneys, and brain.
Fabry disease, an X-linked disorder of glycosphingolipids that is caused by mutations of the GLA gene that codes for α-galactosidase A, leads to dysfunction of many cell types and includes a systemic vasculopathy.
Vasculopathy in the α-galactosidase A null mouse is manifested as oxidant-induced thrombosis, accelerated atherogenesis, and impaired arterial reactivity.
Deregulation of key endothelial pathways as observed in FD vasculopathy is likely caused by intracellular Gb3 accumulation rather than deficiency of GLA.