What Are the Symptoms of Fabry Disease?

Fabry disease is a rare genetic disorder that results in an absence of a particular enzyme that breaks down lipids (National Institute of Neurological Disorders and Stroke). The disease was first discovered in 1898 by two physicians working independently: William Anderson in England and Johann Fabry in Germany (National Tay-Sachs & Allied Diseases Association). The gene for Fabry disease is linked to the X chromosome, so women may carry the gene without showing symptoms. Testing can identify women who are carriers and genetic counseling can help couples with a family history of the disease make important family planning decisions.

What is Fabry Disease?

• Fabry disease is caused by a genetic mutation on the X chromosome. According to the National Institute of Neurological Disorders and Stroke, the mutation causes a lack of ceramide trihexodidase (or alpha-galactosidase-A), an enzyme necessary to break down lipids, a fatty substance in the blood. If the enzyme is lacking or not properly active, lipids build up in the blood vessels, nervous system and eyes eventually causing heart or kidney disease, heart attack or stroke. The genetic mutation is carried on the X chromosome. If present in men, who have one X and one Y chromosome, the mutation always causes Fabry disease; in women, who have two X chromosomes, the mutation must be on both chromosomes to cause the disease. Some women with only one mutated X chromosome may carry the disease and have no outward symptoms. Symptoms may vary for men and women, with men usually having more severe symptoms. The symptoms first begin in childhood or adolescence, although they are often ignored until the adult years when heart or kidney disease is discovered.

Symptoms: Children

• The earliest sign of Fabry disease in children is pain and angiokeratomas, or small, raised reddish-purple spots on the skin (Fabry Support and Information Group [FSIG]). Heart and kidney impairment may already be starting. Other symptoms in children include inability to sweat, gastrointestinal symptoms similar to inflammatory bowel disease (that is, abdominal pain and diarrhea or frequent bowel movements), recurring nausea and vomiting, vertigo, ringing in the ears, headaches or fever.

Symptoms: Men

• In men, Fabry disease is characterized by a burning pain in the hands and feet and angiokeratomas, especially on the lower abdomen and upper thighs (FSIG). Exercise, stress, weather changes or fatigue may aggravate the pain. Men may also experience abdominal discomfort, frequent bowel movements, ringing in the ears, joint pain and back pain, especially in the kidney region. The corneas may be cloudy but vision will be unaffected. Fabry disease eventually impairs heart and kidney function. This impairment usually occurs between 30 to 45 years of age. Men with Fabry disease often have mitral valve prolapse, although this is not specific to Fabry disease.

Symptoms: Women

• Some women are carriers of the genetic mutation with no symptoms whereas others may have symptoms ranging from slight to severe (FSIG). Corneal abnormalities are the most common symptom among women. Other symptoms in women include absence of sweating, angiokeratomas, tingling or pain in the hands or feet, gastrointestinal disorders, lesions in the conjunctiva and retina, ringing in the ears, vertigo, cardiovascular abnormalities and fatigue. Fabry disease often is misdiagnosed as lupus.

Treatment

• Fabry disease is progressive and results in a higher risk for heart attack, heart disease and kidney disease (National Institute of Neurological Disorders and Stroke). Enzyme replacement therapy is available and anticonvulsants (phenytoin and carbamazepine) effectively relieve the pain. Metoclopramide relieves gastrointestinal symptoms. In severe cases, dialysis or kidney transplants are necessary.