Fabry Disease

Fabry disease is an X-linked lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A, leading to progressive accumulation of globotriaosylceramide in cells throughout the body. This substrate accumulation damages the vascular endothelium, resulting in progressive dysfunction of multiple organ systems. Males typically present in childhood with severe acrodystesthesia (burning pain in extremities), angiokeratomas (characteristic dark skin lesions), and ocular manifestations. Without treatment, progressive proteinuria and chronic kidney disease develop, often requiring dialysis or transplantation by the third or fourth decade. Cardiac manifestations include left ventricular hypertrophy, arrhythmias, and premature cardiovascular events. Females with Fabry disease have more variable presentations due to X-inactivation patterns but can develop serious complications. Enzyme replacement therapy (imiglucerase, agalsidase) and substrate reduction therapy (migalastat) can slow disease progression when initiated early.