ABSTRACT
Fabry disease was first described in 1898 independently by Anderson [1] in England and Fabry [2] in Germany. The latter name has become its designation [3], possibly because Fabry continued to publish information about his patient over a 32-year period [4]. Anderson and Fabry each recognized the systemic nature of the disease but, as dermatologists, their focus was on the cutaneous angiokeratomas by which the patient is so readily recognized. The disease is also known as angiokeratoma corporis diffusum universale [5-7]. It was first noted to be X-linked by Opitz and colleagues in 1965 [7]. The disorder was appropriately classified as a glycosphingolipidosis following the isolation and characterization by Sweeley and Klionsky [8] of the Fabry lipid as galactosylgalactosylglucosylceramide (Figure 89.1). The molecular defect was demonstrated by Brady and colleagues [9] as an inability to cleave the terminal galactose from this ceramide trihexoside; thus the defective activity is ceramide trihexosidase (Figure 89.1). The defective enzyme was shown by Kint [10] by means of an artificial substrate to be an -galactosidase. It is referred to as -galactosidase A to distinguish it from the -N-acetylgalactosaminidase which is deficient in Schindler disease and is also an -galactosidase (B). The gene is on the X chromosome at Xq22.1 [11]; the gene has been cloned and its sequence determined [12-14]. A large number and variety of mutations have been defined.
