Distinctive facial features, eye problems, and episodes of severe pain and tingling in the hands and feet are among the main symptoms experienced by people with Fabry disease, a genetic condition caused by the toxic buildup of fatty molecules in small blood vessels and most tissues of the body. The rare disorder particularly affects patients’ hearts, kidneys, skin, and central nervous system — the brain and spinal cord.
The age of onset and severity of symptoms differ among patients. Those with the classic type of Fabry disease usually have progressive and severe symptoms, typically beginning in childhood or adolescence. Patients with the later-onset (atypical) form often have milder symptoms, predominantly limited to a single organ, such as the kidneys or the heart.
While the disease occurs in both sexes, males are generally more severely affected than females, who may live their entire lives without any signs of disease. On average, the life expectancy of untreated patients with Fabry is 10 to 20 years shorter than that of people without the disease.
Both males and females with Fabry disease may have distinctive facial features, such as a recessed forehead, fullness around the eye sockets, bushy eyebrows, and coarse features. It also is common for those with Fabry to have pronounced nose and ear lobules, thickened lips, and a prominent jaw.
Nervous system symptoms
Episodes of severe pain and burning, and tingling sensations in the hands and feet are caused by nerve cell damage and also are very common. These episodes, known as “Fabry crises,” usually start earlier in males — between the ages of 2–8 years — and may be triggered by exercise, fatigue, stress, and fever.
Fabry patients also may show abnormalities, mostly in the form of a whorl-like haze, in the cornea, the transparent layer forming the front of the eye. Blood vessels in the eyes also may appear twisted and/or slightly enlarged. While these eye conditions do not usually affect vision, they are considered important for early diagnosis and monitoring of the disease.
In people with Fabry, fatty molecules known as globotriaosylceramide (Gb3 or GL-3) build up to toxic levels in the small blood vessels and most tissues of the body.
As a result of Gb3 accumulation in skin blood vessels, most patients show clusters of small, reddish or dark-blue spots on the skin, called angiokeratomas. These are mainly found in the area between the belly button and the knees and become larger and more numerous with age.
Broken blood capillaries also are commonly found in the face, lips, and mouth. Many patients also have dry mouth, a condition in which the salivary glands in the mouth don’t make enough saliva.
Sweating abnormalities, such as absent (anhidrosis) and reduced (hypohidrosis) sweat production, also are common, and occur more frequently in males with Fabry. These abnormalities usually lead to dry skin, heat intolerance, or fever of unknown origin. Excessive sweating (hyperhidrosis) also has been reported, but less frequently.
Many Fabry disease patients experience gastrointestinal symptoms such as diarrhea, abdominal cramping, frequent bowel movements, flatulence, early satiety or having a feeling of fullness earlier than normal, reduced appetite, nausea, and/or vomiting.
Hearing problems, including ringing in the ears (tinnitus), vertigo with nausea and dizziness, and progressive or sudden hearing loss also are often present. Such problems are believed to be caused by a narrowing and blockage of blood vessels in the inner year, due to an accumulation of Gb3 in those vessels.
Progressive kidney damage is usually associated with the disease and can lead to kidney failure later in life, especially among males with classic Fabry. These male patients may need dialysis or a kidney transplant by ages 35 to 45. In female patients, kidney involvement is highly variable.
Among people with later-onset Fabry disease, kidney problems usually occur around age 40 in men and may not occur at all in women.
Heart involvement is common among people with Fabry disease. It may include enlargement of the left ventricle of the heart, leakage of blood backward through the heart valve, excessive thickening of the heart muscle, irregular heartbeat, and eventual heart failure.
Again, similar heart problems may occur in men with atypical Fabry, but at older ages.
The occurrence of such symptoms in women with this form of the disease is unclear.
Some patients, particularly those with classic disease, may develop problems in the blood supply of the brain, leading to a stroke. These events are more commonly reported in or after the fourth decade of life, but can also occur in younger patients.
Respiratory symptoms, such as shortness of breath, wheezing, and dry cough, also can develop with progressive disease, likely associated with heart damage. In rare cases, patients may have scarring of lung tissue and airway obstruction.
Other general symptoms that may be associated with Fabry disease include delayed puberty and lack of or sparse hair growth. Malformations of the joints and fingers, swelling in the feet and legs, chronic fatigue, dizziness, headache, and generalized weakness also may occur.
Last updated: May 25, 2021
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