A rare genetic disorder called Fabry disease affects the body's ability to breakdown a type of fat called globotriaosylceramide (Gb3). As the fat builds up in various organs and tissues, Fabry disease can cause a variety of symptoms and complications. An X-chromosome mutation in the GLA gene causes Fabry disease. This gene produces the enzyme alpha-galactosidase A, which breaks down Gb3. As a result of reduced or absent levels of this enzyme in people with Fabry disease, Gb3 builds up in their bodies.
An X chromosome mutation causes Fabry disease. There are two copies of this gene in males and people assigned male at birth (AMAB), while females and individuals assigned female at birth (AFAB) inherit it in an X-linked pattern. Fabry disease is caused by inheriting a mutated copy of the gene from a male or individual AMAB, while Fabry disease is caused by inheriting a mutated copy and a normal copy from a female or individual AFAB. Fabry disease symptoms depend on how the mutation affects enzyme activity and how the two copies of the gene are expressed.
There are two main types of Fabry disease: classic and late-onset. The symptoms vary depending on the type, severity, and age of onset of the disease. Classical Fabry disease usually begins in childhood or adolescence, whereas late-onset Fabry disease usually starts in adulthood. Symptoms of Fabry disease include:
Pain, burning, tingling, or numbness in the hands and feet, especially during exercise, stress, or changes in temperature. This is caused by damage to the nerves that sense pain and temperature.
Red or purple spots on the skin, especially on the lower abdomen, thighs, buttocks, and groin. These are called angiokeratomas and are caused by enlarged blood vessels under the skin.
Reduced sweating or inability to sweat, which can lead to overheating, fever, or heat stroke. This is caused by damage to the sweat glands.
Cloudiness or opacity in the front part of the eye, called the cornea. This does not affect vision, but can be seen by an eye doctor. This is caused by deposits of Gb3 in the cornea.
Gastrointestinal problems, such as nausea, vomiting, diarrhea, constipation, bloating, or abdominal pain. This is caused by damage to the digestive system.
Hearing loss or ringing in the ears, called tinnitus. This is caused by damage to the inner ear or the nerves that carry sound signals to the brain.
Heart problems, such as enlarged heart, irregular heartbeat, chest pain, shortness of breath, or heart failure. This is caused by damage to the heart muscle or the valves that control blood flow.
Kidney problems, such as protein or blood in the urine, reduced urine output, swelling in the legs or feet, or kidney failure. This is caused by damage to the kidney filters or the tubes that carry urine out of the body.
Brain problems, such as headaches, dizziness, stroke, seizures, or cognitive impairment. This is caused by damage to the blood vessels or the nerve cells in the brain.
Fabry disease can be diagnosed by a combination of medical history, physical examination, blood tests, genetic tests, and organ function tests. The diagnosis may include:
Medical history: The doctor will ask about the symptoms, family history, and any medications or supplements that the person is taking.
Physical examination: The doctor will look for signs of Fabry disease, such as angiokeratomas, corneal cloudiness, enlarged heart, or kidney damage.
Blood tests: The doctor will measure the level of alpha-galactosidase A enzyme in the blood. In males and people with AMAB, the enzyme level is usually low or absent. Depending on the type of mutation and gene expression, the enzyme level may be normal or low in females and people with AFAB.
For genetic tests, a blood sample or cheek swab will be used to test for the GLA gene mutation. Both males and people with AMAB and females and people with AFAB can be diagnosed with Fabry disease using this test, and carriers can also be identified.
Fabry disease affects the heart, kidneys, and brain, so the doctor will perform tests to determine how well these organs are functioning. Electrocardiograms (ECGs), echocardiograms, urine analyses, kidney biopsy tests, magnetic resonance imaging (MRI), and computed tomography (CT) may be performed.
There is no cure for Fabry disease, but treatments are available to help manage the symptoms and prevent or delay the complications. The treatment options may include:
By injecting a synthetic version of the alpha-galactosidase A enzyme into the bloodstream, enzyme replacement therapy (ERT) helps break down Gb3 and reduce its accumulation in the organs and tissues. In people with Fabry disease, ERT can improve pain, sweating, gastrointestinal problems, hearing loss, and organ function. The drug is given by intravenous infusion at a hospital or clinic every two weeks.
As part of oral chaperone therapy, a pill is taken to bind to the enzyme alpha-galactosidase A and help it fold correctly and function better. As a result, Gb3 is broken down and its accumulation in the organs and tissues is reduced. The pain, sweating, gastrointestinal issues, hearing loss, and organ function of people with Fabry disease can be improved with oral chaperone therapy, which is taken at home once or twice a day.
Medications for pain and burning sensations in the hands and feet are available as part of this treatment. As needed, pain medication can be taken at home by mouth, such as ibuprofen, naproxen, or carbamazepine or gabapentin, which are anti-inflammatory and anticonvulsant drugs.
In this treatment, drugs are taken to treat or prevent Fabry disease complications, such as heart disease, stroke, or kidney failure. Blood pressure drugs, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), blood thinners, such as aspirin or warfarin, and cholesterol-lowering drugs, such as statins, may be included in this list. In addition, other medications are taken at home according to their prescriptions.
An organ transplant is a procedure that involves replacing a damaged organ with a healthy one from a donor, such as the heart or kidney. By performing an organ transplant in a hospital, the patient can restore its function and improve their quality of life.
In spite of the fact that Fabry disease is a genetic condition, people with the disease or carriers of the condition can take steps to reduce the risk of passing it on to their children. These steps may include:
Information and guidance are provided to people with genetic disorders or at risk of developing them by genetic counselors. A genetic counselor can help people understand the inheritance pattern, the risks, and the options for Fabry disease. A genetic counselor can also help people make informed decisions about family planning and testing.
During pregnancy, this test detects the presence or absence of the mutation in the GLA gene in the fetus. In order to prepare for the birth of a child with Fabry disease or make decisions about whether to continue the pregnancy or terminate it, parents should undergo prenatal testing. DNA is extracted from placenta or amniotic fluid during prenatal testing.
During in vitro fertilization (IVF), preimplantation genetic diagnosis (PGD) can be performed in order to select embryos that do not have the mutation in the GLA gene before implanting them. PGD can help parents have a child without Fabry disease or avoid having a child with Fabry disease. It is performed by analyzing the DNA of a single embryo cell.
The outlook for Fabry disease depends on the type, severity, and age of onset, as well as the availability and effectiveness of the treatments. Due to the complications associated with Fabry disease, such as heart attacks, strokes, and kidney failure, people with the disease may have a shorter life expectancy. When diagnosed early and treated appropriately, people with Fabry disease can live a longer and healthier life. For Fabry disease patients, regular checkups and follow-up tests are necessary to monitor their condition and adjust their treatment as necessary. The overall health and well-being of people with Fabry disease can also be improved by adopting a healthy lifestyle, which includes eating a balanced diet, exercising regularly, avoiding tobacco and alcohol, and managing stress.
