Fabry Disease
(Alpha-Galactosidase A Deficiency; Anderson-Fabry Disease; Angiokeratoma Corporis Diffusum; Angiokeratoma Diffuse; Ceramide Trihexosidase Deficiency; GLA Deficiency; Glycolipid Lipidosis; Hereditary Dystopic Lipidosis)
Definition
Fabry disease is an inherited genetic disorder caused by a defective gene. The disease causes fatty deposits in several organs of the body.
Males who inherit the defective gene will express the disease. Females who have a single copy of the gene are called "carriers" and most are asymptomatic (do not have symptoms). However, some women do have symptoms, and the severity of these symptoms can vary widely. On occasion, women may be as severely affected as men.
Causes
Fabry disease is caused by a deficiency of the enzyme alpha galactosidase-A (GALA, also known as ceramide trihexosidase). GALA usually works to clear fatty substances called glycosphingolipids from the body. However, in Fabry disease, the absence of GALA causes this fatty substance to accumulate in the blood and blood vessel walls. This leads to constriction of blood flow through the vessels. Eventually, the decreased blood flow leads to problems of the skin, kidneys, heart, and nervous system.
Risk Factors
The primary risk factor is having family members with the disease or who are carriers of the disease.
Symptoms
Symptoms may begin in childhood or early adulthood. Common symptoms include:
- Pain and burning sensations in the hands and feet, often provoked by exercise, fatigue, or fever
- Spotted, dark red skin lesions (angiokeratomas) that generally are found in the area between the belly button and the knees (they may also be found elsewhere)
- Inability to sweat
- Changes in the eyes (corneal opacities, cataracts)
Cataracts
As adults, males may experience the following symptoms due to blood vessel blockage:
- Kidney problems, often requiring dialysis or transplant
- Risk of early stroke or heart attack
- Chest pain
- High blood pressure
- Heart failure, left ventricular hypertrophy
- Mitral valve prolapse or insufficiency
- Frequent bowel movements after eating
- Diarrhea
- Joint or back pain
- Ringing in the ears ( tinnitus) or dizziness ( vertigo)
- Chronic bronchitis or shortness of breath
- Osteoporosis
- Delayed puberty or delayed growth
Stroke
Diagnosis
Your doctor will ask about your symptoms and medical history, and perform a physical exam. Diagnosis is usually made on the basis of the symptoms listed above. A test to measure the enzyme GALA or DNA analysis can confirm Fabry disease.
Treatment
While there is no cure for Fabry disease, there is a medicine approved by the Food and Drug Administration (FDA) to treat the condition. Agalsidase beta (Fabrazyme) is an enzyme replacement therapy that is given intravenously (via a needle that is placed into your arm).
Treatment may also involve other medicines and procedures to reduce symptoms.
To Treat Pain
- Carbamazepine
(Tegretol)
- According to the Food and Drug Administration (FDA), patients of Asian ancestry who have a certain gene, called HLA-B*1502, and take carbamazepine are at risk for dangerous or even fatal skin reactions. If you are of Asian descent, the FDA recommends that you get tested for this gene before taking carbamazepine. If you have been taking this medication for a few months with no skin reactions, then you are at low risk of developing these reactions. Talk to your doctor before stopping this medication.
- Phenytoin (Dilantin)
- Neurontin
Prevention
There is no known way to prevent Fabry disease. If you have Fabry disease or have a family history of the disorder, you can talk to a genetic counselor when deciding to have children.
Fabry Support and Information Group (FSIG)
National Institute of Neurological Disorders and Stroke
National Tay-Sachs and Allied Diseases Association
Canadian Fabry Association
Fabry Society of Canada
Fabry disease: medications. EBSCO DynaMed website. Available at: http://www.ebscohost.com/dynamed/. Updated August 2011. Accessed December 2, 2011.
Fabry Support and Information Group website. Available at: http://www.fabry.org.
Martins AM, D’Almeida V, Kyosen SO, et al. Guidelines to diagnosis and monitoring of Fabry disease and review of treatment experiences. J Pediatrics. 2009;155(4 Suppl):S19-S31.
National Institute of Neurological Disorders and Stroke website. Available at: http://www.ninds.nih.gov.
Nelson Textbook of Pediatrics. 18th ed. WB Saunders; 2007.
12/20/2007 DynaMed's Systematic Literature Surveillance http://www.ebscohost.com/dynamed/what.php: 2007 safety alerts for drugs, biologics, medical devices, and dietary supplements: Carbamazepine (marketed as Carbatrol, Equetro, Tegretol and generics). Medwatch. US Food and Drug Administration website. Available at: http://www.fda.gov/medwatch/safety/2007/safety07.htm#carbamazepine.
Last reviewed December 2011 by Kari Kassir, MD
Please be aware that this information is provided to supplement the care provided by your physician. It is neither intended nor implied to be a substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the advice of your physician or other qualified health provider prior to starting any new treatment or with any questions you may have regarding a medical condition.
