Fabry Disease

Fabry Disease
Fabry Disease

Overview Of Fabry Disease

Fabry disease is an inherited disorder that results from the buildup of a particular type of fat, called globotriaosylceramide, in the body’s cells. Beginning in childhood, this buildup causes signs and symptoms that affect many parts of the body. Characteristic features of Fabry disease include episodes of pain, particularly in the hands and feet (acroparesthesias); clusters of small, dark red spots on the skin called angiokeratomas; a decreased ability to sweat (hypohidrosis); cloudiness or streaks in the front part of the eye (corneal opacity or corneal verticillata); problems with the gastrointestinal system; ringing in the ears (tinnitus); and hearing loss. Fabry disease also involves potentially life-threatening complications such as progressive kidney damage, heart attack, and stroke. Some affected individuals have milder forms of the disorder that appear later in life and affect only the heart or kidneys.

Commonly Associated With

  • alpha-galactosidase A deficiency
  • Anderson-Fabry disease
  • angiokeratoma corporis diffusum
  • angiokeratoma diffuse
  • ceramide trihexosidase deficiency
  • Fabry’s disease
  • GLA deficiency
  • hereditary dystopic lipidosis

Causes Of Fabry Disease

Fabry disease is caused by mutations in the GLA gene. This gene provides instructions for making an enzyme called alpha-galactosidase A. This enzyme is active in lysosomes, which are structures that serve as recycling centers within cells. Alpha-galactosidase A normally breaks down a fatty substance called globotriaosylceramide. Mutations in the GLA gene alter the structure and function of the enzyme, preventing it from breaking down this substance effectively. As a result, globotriaosylceramide builds up in cells throughout the body, particularly cells lining blood vessels in the skin and cells in the kidneys, heart, and nervous system. The progressive accumulation of this substance damages cells, leading to the varied signs and symptoms of Fabry disease.

GLA gene mutations that result in an absence of alpha-galactosidase A activity lead to the classic, severe form of Fabry disease. Mutations that decrease but do not eliminate the enzyme’s activity usually cause the milder, late-onset forms of Fabry disease that typically affect only the heart or kidneys.

Symptoms Of Fabry Disease

Fabry disease can have many symptoms because it affects cells throughout the body. The symptoms include:

• Chronic pain — usually a burning or tingling sensation — in the hands and feet. The pain sometimes briefly becomes more intense, requiring medication to bring it down to manageable levels. The pain can go away in adulthood.

• Clusters of small, dark red spots in various locations on the skin.

• Opaque corneas, resulting in cloudy-looking eyes and problems with eyesight.

• Ringing in the ears, and hearing loss.

• Kidney damage, which worsens over time, becoming serious.

• Increased risk of life-threatening heart attacks and stroke.

• A variety of gastrointestinal problems.

• A decreased ability to sweat.

These symptoms usually appear in infancy or childhood, though in rarer mild cases they will begin in adulthood and be less severe.

Treatment Of Fabry Disease

For the most part, treatment of Fabry disease focuses on medications that improve the patient’s quality of life. Pain relievers, including Tegretol and Dilantin, are used to combat episodes of intense pain. Gastrointestinal problems may be remedied with pancrelipase.

Other medications are used to prevent symptoms from becoming life-threatening. Heart and anti-clotting medications may be used along with pacemakers to prevent heart attacks. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are used to combat kidney disease. In more advanced stages of kidney disease, dialysis or a kidney transplant are options.

Special diets that cut back on fats and salts may also be considered because they can reduce the intensity of some symptoms.


At first, Fabry disease can resemble normal growing pains or arthritis, but other symptoms start to appear with time.

Fabry can be confirmed with a test measuring levels of alpha-galactosidase. If doctors find low levels of the enzyme, they may ask for genetic testing for the mutated GLA gene. Genetic testing may also be recommended for close family members who do not show any symptoms.