α-Galactosidase A Deficiency: Fabry Disease

Abstract Fabry disease is a rare, inborn error of glycosphingolipid catabolism, inherited as an Xlinked recessive disorder with an incidence of only 1 in 40,000. Deficient activity of the lysosomal hydrolase, cx-galactosidase A, causes a symptom complex of acroparesthesias, angiokeratoma, corneal and lenticular opacities, and anhidrosis. In 1897, two dermatologists independently described the condition: Fabry in Germany and Anderson in Great Britain. Fabry disease is the preferred eponymic designation used in most places in the world, except in England where is it called Anderson-Fabry disease. The disorder is sometimes referred to as angiokeratoma corporis diffusum, especially in the dermatology literature. The clinical manifestations result from accumulation of neutral glycosphingolipids, with cx-galactosyl moieties, in the lysosomes of vascular endothelial and smooth muscle cells, pericytes, fibroblasts, and perineurial cells. There are no deposits of glycosphingolipids in Schwann cells or axons. Damage to the blood vessels of the brain, heart, and kidney is potentially life threatening. In the peripheral nerve, a severe painful neuropathy results. The deposits in the skin and eye cause the characteristic hallmarks of the disease, angiokeratomas and lens opacities. The predominant glycosphingolipid that accumulates is globotriaosylceramide (Fig. 25-1), with lesser amounts of galabiosylceramide. In patients with B or AB blood types, the cx-galactosyl moieties of blood group B contribute to the total pool of glycosphingolipid deposition.