Contributors: Brian P. Brooks and Alan Sugar
Fabry disease (Fabry syndrome, angiokeratoma corporis diffusum, Anderson-Fabry disease, hereditary dystopic lipidosis, alpha-galactosidase A deficiency, GLA deficiency, ceramide trihexosidase deficiency, OMIM # 301500) is an X-linked recessive syndrome caused by mutations in the GLA gene. Characteristic lesions appear early in life involve the skin (angiokeratomas, hypohidrosis), nervous system (acral pain, paresthesias), kidney (renal failure), cardiovascular system, gastrointestinal tract and eye. Other major clinical signs include burning pains in the extremities, fever, and renal dysfunction, most of them developing in childhood or early adolescence. With increasing age, burning pains throughout the body become more frequent and severe. A characteristic of this lipidosis is the accumulation of ceramide trihexoside and related neutral glycosphingolipids with terminal α-galactosyl moieties throughout the cardiovascular system and kidneys due to a deficiency of alpha-galactosidase A. These sphingolipids are progressively deposited in the vascular endothelium, smooth muscle of blood vessels, and cells of the glomeruli, and in numerous other tissues, including the corneal epithelium and lens. The most striking ocular manifestation is cornea verticillata, which occurs in virtually all affected males. Other ocular abnormalities in Fabry disease include a star-shaped opacities in the posterior region of the lens, edema of the eyelids (edema), a tortuosity, dilatations, and aneurysms in blood vessels of the retina and conjunctiva. Visual acuity is usually not impaired, but one case report describes a 16-year-old boy with Fabry disease who suffered sudden visual loss secondary to a central retinal artery occlusion. The earliest ocular manifestation appears to be the presence of subtle lens opacities.