Cerebrovascular complications of fabry's disease

Fabry's disease (FD), or angiokeratoma corporis diffusum, is a rare X-linked inherited disorder of glycosphingolipid metabolism (Desnick et al., 2001). Deficiency of a lysosomal hydrolase, a-galactosidase, leads to progressive accumulation of glycosphingolipids (mainly ceramide trihexoside) in most visceral tissues and primarily in the lysosomes of the vascular endothelium. Progressive endothelial glycosphingolipid accumulation results in tissue ischemia and infarction, and leads to the major clinical manifestations of the disease (Desnick et al., 2001). The disease is genetically heterogeneous, as it has been linked to multiple mutations in the a-galactosidase gene (Chen et al., 1998; Takenaka et al., 1996; Topaloglou et al., 1999). While the prevalence of FD has been estimated to be around 1 in 40 000 males (Desnick et al., 2001), a recent study (Spada et al., 2006) found 12 of 37 104 consecutive male neonates with specific mutations in the a-galactosidase gene. This prevalence of 1 in 3 100 males suggests a vast underdiagnosis of FD. Hemizygote males usually have characteristic skin lesions and angiokeratomas, and often have unexplained fever, acroparesthesias, episodic crises of excruciating pain, corneal and lenticular opacities, hypohidrosis, and cardiac and renal dysfunction (Desnick et al., 2001). Tinnitus and hearing loss are also very common. Death usually occurs in adult life from renal, cardiac, and/or cerebral complications of their vascular disease (Desnick et al., 2001). Heterozygote females either are asymptomatic or exhibit fewer signs and symptoms of the disease, although occasional females have been described with symptoms similar to males (Bird and Lagunoff, 1978).