Fabry disease is caused by the lack of or faulty enzyme needed to metabolize lipids, fat-like substances that include oils, waxes, and fatty acids. The enzyme is known as ceramide trihexosidase, also called alpha-galactosidase-A.

A mutation in the gene that controls this enzyme causes insufficient breakdown of lipids, which build up to harmful levels in the eyes, kidneys, autonomic nervous system, and cardiovascular system.

Fabry disease is one of several lipid storage disorders and the only X-linked lipid storage disease. Since the gene that is altered is carried on a mother’s X chromosome, her sons have a 50 percent chance of inheriting the disorder and her daughters have a 50 percent chance of being a carrier. Some women who carry the genetic mutation may have symptoms of the disease.

Symptoms usually begin during childhood or adolescence and include:

• Burning sensations in the hands that gets worse with exercise and hot weather
• Small, non-cancerous, raised reddish-purple blemishes on the skin
• Eye manifestations, especially cloudiness of the cornea

Lipid storage may lead to impaired arterial circulation and increased risk of heart attack or stroke. The heart may also become enlarged and the kidneys may become progressively involved. Other symptoms include:

• Decreased sweating
• Fever
• Gastrointestinal difficulties, particularly after eating

Patients with Fabry disease often survive into adulthood but are at increased risk of strokes, heart attack and heart disease, and renal failure.

Enzyme replacement therapy can reduce lipid storage, ease pain, and improve organ function. The pain in the hands and feet usually responds to anticonvulsants such as phenytoin and carbamazepine. Gastrointestinal hyperactivity may be treated with metoclopramide. Some individuals may require dialysis or kidney transplantation.