Fabry disease.

More than a hundred years ago, in 1898, two dermatologists, William Anderson in England and Johannes Fabry in Germany, independently reported on patients with multiple angiokeratomas as well as some other symptoms. Today, the disease is called Anderson-Fabry or only Fabry disease, or angiokeratoma corporis diffusum, the latter being more often found in dermatologic literature. Fabry disease is a rare X-linked disorder caused by deficient activity of the lysosomal enzyme αgalactosidase A, characterized by angiokeratomas in the skin, along with severe multiorgan dysfunction and premature death. The estimated incidence of this panethnic disease is 1:40,000 in male or 1:117,000 in the general population. The defective gene is located on chromosome Xq2122 and encodes for α-galactosidae. The lack of this enzyme activity results in progressive accumulation of neutral glycosphingolipids, primarily globotriaosylceramide (Gb3), within lysosomes of cells in various organ systems, leading to a wide variety of progressive clinical manifestations in affected individuals. The accumulation of Gb3 leads to various symptoms, which appear in different periods of life. The earliest symptoms are usually pain and angiokeratomas that appear in childhood or adolescence, the progression of disease being associated with cardiac, cerebral and vascular involvement. The symptoms that can raise suspicion of Fabry disease are early stroke, left ventricular hypertrophy, hypohidrosis, renal insufficiency, acroparesthesias and angiokeratomas.