Overview

Fabry disease is an inherited disorder that results from the buildup of a particular type of fat in the body’s cells, called globotriaosylceramide or GL-3. Fabry disease affects many parts of the body. Signs and symptoms may 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 of the front part of the eye (corneal opacity); and hearing loss. Potentially severe complications can include progressive kidney damage, heart attack, and stroke. Milder forms of the disorder may appear later in life and affect only the heart or kidneys. Fabry disease is caused by mutations in the GLA gene and is inherited in an X-linked manner. Treatment may include enzyme replacement therapy (ERT); pain medications, ACE inhibitors; and chronic hemodialysis or renal transplantation for end stage renal disease.

Symptoms

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, and
  • Small, raised reddish-purple blemishes on the skin.

Some boys will also have 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
  • Fabry disease is one of several lipid storage disorders
  • Abdominal pain
  • Anemia
  • Arthralgia
  • Arthritis
  • Cerebral ischemia
  • Congestive heart failure
  • Conjunctival telangiectasia
  • Corneal dystrophy
  • Hematuria
  • Hyperkeratosis
  • Hypohidrosis
  • Malabsorption
  • Myalgia
  • Nephrotic syndrome
  • Opacification of the corneal stroma
  • Paresthesia
  • Renal insufficiency
  • Telangiectasia of the skin

Causes

Fabry disease is an inherited disorder where the defective gene is located on the X-chromosome. Females have two X chromosomes, one inherited from each of their parents. Males have one X chromosome inherited from their mother and one Y chromosome inherited from their father.

A female with Fabry receive one X chromosome with a defective gene and one X chromosome with the normal gene, and thus often has some protection from the major manifestations of the disease. This is not always the case though as there is a high degree of variability in females. Males with Fabry disease receive only one abnormal X chromosome that contains the abnormal gene and thus express the disease.

All male and female children of an affected female have a 50% chance of inheriting the defective gene from their mother. If the father is the one carrying the Fabry gene all female children will inherit the defective gene and all male children will not. The inheritance pattern of Fabry disease is called X-linked inheritance. Fabry disease occurs in all ethnic groups. It is estimated that one person in 40,000 has Fabry disease.

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,regardless of their sex, when deciding to have children.

Fabry disease is inherited in an X-linked pattern, which means that the gene that causes the condition is located on the X chromosome. In males (who have only one X chromosome), one mutated copy of the gene is enough to cause symptoms of the condition. Because females have two copies of the X chromosome, one mutated copy of the gene in each cell usually leads to less severe symptoms in females than in males, or may cause no symptoms at all.

Diagnosis

An early diagnosis of  Fabry disease is useful for many reasons, including starting symptom management, reducing the risk of further problems happening as well as early identification of other family members who may be affected.

Initially, a combination of the signs and symptoms may lead your doctor to think you may have Fabry disease. Your doctor may then refer you to a specialist centre for a diagnosis of Fabry disease to be confirmed and for any treatment to be initiated.

Anyone who is thought to have Fabry disease can have the diagnosis confirmed through laboratory testing. In males this can be done by taking a blood sample which is then tested to check the level of the a-Gal A enzyme. If the level of the enzyme is very low a diagnosis of Fabry disease can be made. This test can also be used to confirm the diagnosis of Fabry disease in females, although a laboratory genetic test in which DNA is analysed is a more effective test for confirming the diagnosis in women especially where there is a family history of Fabry disease.

Prenatal diagnosis is possible by measuring the a-Gal A activity in tissue or fluid taken from around the foetus. This test may be offered to expectant mothers who have Fabry disease. Specialist support and advice are available for such testing (see who can help).

An examination of your family history may indicate the presence of Fabry disease, particularly if a male relative suffered from kidney failure, heart disease or stroke early in life. To help identify whether there is the possibility of you or any of your relatives having Fabry disease, you can complete a medical family tree.

Prognosis

Patients with Fabry disease often survive into adulthood but are at increase risk of strokes, heart attack and heart disease, and kidney failure. The life expectancy of males with Fabry disease is estimated to be approximately 40 -60 years.