Fabry disease is a rare, inherited disease caused by the deficiency of an enzyme. It is a lipid storage disorder that mainly affects males.
The disease can cause long-term difficulties in the kidneys, heart, and nervous system. It can be fatal.
Other names include Anderson-Fabry disease, alpha-galactosidase A deficiency, or angiokeratoma corporis diffusum.
Type 1 or Classic Fabry disease starts at a younger age, and it is estimated to affect 1 in every 40 to 60,000 males. Many more carry the defective gene without symptoms.
Type 2 or Later-onset Fabry disease can occur as frequently as 1 in 1,500 to 4000 males.
Fabry disease may be hard to detect, because several of its signs and symptoms overlap those present in other conditions.
Patients do not typically have all of the symptoms associated with Fabry at once, and these symptoms may develop at different times throughout their lives.
It is important that the doctor finds out whether there is a family history of Fabry disease whenever it is suspected.
Females rarely show serious symptoms of Fabry disease, but for some the symptoms can be severe.
Symptoms of Type 1 Fabry disease may include serious eye difficulties, including cloudiness of the cornea, as well as cardiovascular, cerebrovascular, and kidney and stomach issues.
Fabry disease in males
Signs and symptoms usually start during childhood. This is known as classic manifestation of Fabry disease.
These symptoms include:
- Skin rash, known as angiokeratoma: A dark, red, spotted skin rash appears. The rash is seen most densely between the navel (belly button) and the knees.
- Reduced ability to sweat: This is known as hypohidrosis.
- Pain in the hands and feet: Also known as acroparesthesia. This pain can be triggered by stress, fatigue, fever, physical activity, and even changes in the weather.
- Clouding of the corneas: Also called keratopathy. This does not affect vision.
Fabry disease usually develops slowly over many years, as GL-3 gradually accumulates. Symptoms may instead show later in life, known as later-onset manifestation.
Patients may experience:
Gastrointestinal problems, including:
Cardiovascular problems, including:
This happens because years of GL-3 buildup results in damage to the heart and blood vessels that supply the heart. Problems with arterial circulation increase the risk of stroke or heart attack.
Renal, or kidney, problems can result after decades of GL-3 accumulation. There may be renal failure or renal insufficiency. Fabry disease is often first detected when the patient comes to the doctor with kidney problems.
Central nervous system disorders can occur when small blood vessels in the brain become affected after years of GL-3 backup.
Patients have a higher risk of:
Fabry disease in females
Females have either no symptoms or much milder ones than males, as they often carry the gene without being affected. However, a small percentage may experience symptoms as severely as males do.
In more serious cases, females have the same signs and symptoms as males with increased severity.
As females often carry the disease without the gene being activated, it can be difficult to accurately calculate how many females are affected.
Fabry disease results when there is a shortage of an enzyme called alpha-galactosidase A (a-GAL A). This enzyme is is encoded by the GLA gene.
A fault, or mutation in this gene causes a poor breakdown of lipids. This leads to a harmful buildup of lipids – specifically globotriaosylceramide (GL-3) – in the cardiovascular system, autonomic nervous system, kidneys, and eyes.
There are several lipid storage disorders. Fabry disease is the only X-linked, or inherited, one.
The mutated gene is carried in the mother’s X-chromosome, leading to a 50 percent chance she will pass it on to her sons, and a 50 percent risk that her daughters will be carriers.
Controlling or preventing symptoms and complications is the main aim of treatment.
Episodes of pain are nearly always linked to certain triggers, such as exposure to heat, temperature changes, sun exposure, exercise, and fever. The patient must learn to avoid these pain triggers.
For patients with severe and frequent episodes of pain, the doctor may prescribe an anticonvulsant, such as carbamazepine (Tegretol, Tegretol XR, Equetro, Carbatrol) or diphenylhydantoin (Dilantin). They should be taken daily.
Enzyme replacement therapy (ERT) is a medical treatment that replaces an enzyme which is either absent or deficient in patients. In Fabry disease patients’ cases, the missing enzyme is alpha-galactosidase A (a-GAL A).
In the United States, Fabrazyme is the only ERT treatment approved by the U.S. Food and Drug Administration (FDA) for Fabry disease.
The producers, Genzyme Corporate, write on their website “The lowering of GL-3 suggests that Fabrazyme may improve how Fabry disease affects your body; however a relationship of lower GL-3 to specific signs and symptoms of Fabry disease has not been proven.”
The treatment has passed all clinical trials and its safety and effectiveness have been demonstrated. It is, however, expensive.
The other complications related to Fabry disease, such as skin, heart, kidney, and psychological problems are treated separately as they occur, by specialist doctors. For example, heart symptoms will be treated by a cardiologist.
In a 2009 study published in Genetics in Medicine, researchers found that:
“The life expectancy of males with Fabry disease was 58.2 years, compared with 74.7 years in the general population of the United States. The life expectancy of females with Fabry disease was 75.4 years, compared with 80.0 years in the United States.”
Patients who are diagnosed early and can receive treatments promptly have longer lifespans.
The doctor may suspect Fabry disease if the patient has the associated signs and symptoms. If one of the patient’s relatives is found to have the disease, the physician will order a blood test to measure a-GAL A activity.
Screening females for Fabry disease is less simple. The blood test can be misleading, due to the random nature of X-inactivation. X-inactivation means that the faulty gene may be switched off, so the enzyme a-GAL A won’t be affected.
A chromosomal analysis of the GLA gene is more accurate than a blood test.
If excessive GL-3 buildup is detected, a kidney biopsy may help.
Fabry disease is commonly misdiagnosed by pediatricians and internists.