This is a disease caused by a deficiency of alpha-galactosidase A. The disease is transmitted on the X chromosome, and the underlying disorder is an error in glycosphingolipid ceramide trihexoside metabolism. This error in metabolism results in the accumulation of glycosphingolipid ceramide trihexoside in vascular smooth muscle cells, ganglion cells, perineural cells of the autonomic nervous system, reticuloendothelial cells, myocardial and connective tissue cells as well as in cells of the corneal epithelium and renal glomeruli and tubules.
This disease becomes evident during the first decade of life, and it is characterized by the development of skin lesions and pain. Angiokeratoma corporis diffusum refers to clusters of dark red, punctate angiectases that develop symmetrically over the hips, buttocks, thighs, lower abdomen, and lumbar region. Painful attacks of the digits, which may radiate proximally to include the abdomen, are often accompanied by fever and an increased erythrocyte sedimentation rate (ESR). Cardiovascular involvement manifests as coronary artery disease or congestive heart failure (CHF). Lipid deposition in the kidneys results in renal failure, which is the most frequent cause of death in untreated persons. Diagnosis is often made by renal biopsy with findings of lipid vacuoles within the glomerular and tubular epithelium, or by finding alpha-galactosidase deficiency in persons with characteristic symptoms. Treatment is usually symptomatic. Dialysis for renal failure, phenytoin for painful neuropathies, and careful counseling for hypohidrosis-associated heat stroke are treatments. Patients are good candidates for kidney transplants. Laboratory evidence of mildly elevated transaminases are nonspecific and not helpful in establishing the diagnosis.