Fabry Disease Health Article

Definition

Fabry disease is a genetic condition that typically affects males. It is caused by deficiency of an enzyme, a chemical that speeds up another chemical reaction. Fabry disease can affect many parts of the body including the kidneys, eyes, brain, and heart. Pain in the hands and feet and a characteristic rash are classic features of this disease.

Description

The symptoms of Fabry disease were first described by Dr. Johann Fabry and Dr. William Anderson in 1898. The enzyme deficiency that leads to the disease was identified in the 1960s. Fabry disease is caused by a change (mutation) in the GLA gene. This gene is responsible for the production of the enzyme alpha-galactosidase A. Alpha-galactosidase A normally breaks down globotriaosylceramide. Globotriaosylceramide is a natural substance in the body, made of sugar and fat. A mutation in the GLA gene leads to a decrease in alpha-galactosidase A activity which, in turn, leads to an excess of globotriaosylceramide. The excess globotriaosylceramide builds up in blood vessels (veins, arteries, and capillaries) and obstructs normal blood flow. It also builds up in parts of the skin, kidneys, heart, and brain. It is this build-up that inhibits normal function and leads to the symptoms associated with the disease.

The symptoms of Fabry disease are variable. Some individuals with Fabry disease have severe complications, while others have very mild symptoms. The first sign of the disease may be a painful burning sensation in the hands and feet (acroparesthesias). A red rash, most commonly between the belly button and the knees (angiokeratoma) is also common. The outer portion of the eye (cornea) may also become clouded in individuals with Fabry disease. The progressive build up of globotriaosylceramide can also lead to kidney problems and heart disease in adulthood.

Genetic profile

The gene that produces alpha-galactosidase A is located on the X chromosome. It is called the GLA gene. Since the GLA gene is located on the X chromosome, Fabry disease is considered to be X-linked. This means that it generally affects males.

A person's sex is determined by his or her chromosomes. Males have one X chromosome and one Y chromosome. Females, on the other hand, have two X chromosomes. Males who possess a mutation or change in their GLA gene will develop Fabry disease. Females who possess a mutation in one of their GLA genes typically do not develop many of the symptoms associated with Fabry disease. This is because a female's other X chromosome does not have the mutation, and the normal chromosome can take over the function of the abnormal chromosome and keep her from getting the disease. These women are considered to be carriers. If a woman is a carrier, she has a 50% risk with any pregnancy to pass on her X chromosome with the mutation. Therefore, with every male pregnancy she has a 50% risk of having an affected son, and with every female pregnancy she has a 50% risk of having a daughter who is a carrier.

Demographics

Fabry disease affects approximately one in 40,000 live births. It occurs evenly among all ethnic groups. Almost always, only male children are affected. Although female carriers of the disease occasionally develop symptoms of the disease, it is rare for a female carrier to be severely affected.

Signs and symptoms

The signs and symptoms of Fabry disease vary. Some individuals with Fabry disease have many severe symptoms, while other individuals' symptoms may be few and mild. The symptoms typically increase or intensify over time. This progression is caused by the slow buildup of globotriaosylceramide as the person ages.

A painful burning sensation in the hands and feet (acroparesthesias) is one of the first symptoms of Fabry disease. This pain can be severe and may grow worse with exercise, stress, illness, extreme heat, or extreme cold. Another symptom of Fabry disease typically present during childhood is a red rash (angiokeratoma). This rash typically develops between the navel and the knees. Children with Fabry disease may also have a clouding of the outer most portion of the eye (cornea). This symptom is usually diagnosed by an eye doctor (ophthalmologist). The cloudiness may increase with time. A decreased ability to sweat is another common symptom of Fabry disease.

Due to the progressive nature of Fabry disease, most affected individuals develop additional symptoms by age 40. The buildup of globotriaosylceramide in the heart can lead to heart problems. These heart problems can include changes in the size of the heart (left ventricular enlargement), differences in the heart beat, and leaky heart valves. Mitral valve prolapse is a particular type of leaky heart valve that is common in Fabry disease, even in childhood. The excess globotriaosylceramide can also disrupt normal blood flow in the brain. In some cases this can cause dizziness, seizures, and stroke. The kidneys are other organs affected by Fabry disease. Kidney problems can lead to an abnormal amount of protein in the urine (proteinuria). Severe kidney problems can lead to kidney failure.

Although the symptoms of Fabry disease usually occur in males, female carriers may occasionally exhibit symptoms of the disease. Some carriers experience pain in their hands and feet. Carrier females may also have proteinuria and clouding of their cornea. It is rare for a female to experience all of the symptoms associated with Fabry disease.