What is Fabry disease?
Fabry disease is a rare genetic disease a deficiency of the enzyme alpha-galactosidase A (a-Gal A) that causes a buildup of a type of fat called globotriaosylceramide (Gb3, or GL-3) in the body. Fabry disease is classified as a type of lysosomal storage disorder. Lysosomes are isolated areas of cells that contain enzymes. In a lysosomal storage disorder these enzymes do not properly metabolize certain fatty molecules. As a result, the undigested fat molecules accumulate and impair a cell's ability to function. In Fabry disease, the alpha-galactosidase A enzymes are deficient and globotriaosylceramide accumulates, which can affect the function of the skin, eyes, gastrointestinal system, kidney, heart, brain, and nervous system.
Fabry disease is the result of a mutation of the gene responsible for making alpha-galactosidase enzyme, which is located on the X chromosome. Fabry affects mostly males though rarely females may inherit the disease.
Fabry disease is a progressive disorder and symptoms that affect the kidneys, heart, or brain most often occur when patients are age 30 to 45 years.
What is the prevalence of Fabry disease?
It is estimated that Fabry disease affects 1 in 40,000 males. The prevalence of Fabry disease in females is unknown. It can affect all ethnicities, but it predominantly affects Caucasians. Late-onset forms of Fabry disease, which tend to be milder, are more common than the classic severe form diagnosed earlier in life.
What causes Fabry disease? Is it genetic?
- Fabry disease is a genetic disorder. A genetic disorder is caused by a mutation, or change, in a part of a person's DNA.
- In Fabry disease, the defective gene is on the X-chromosome, which is one of two sex chromosomes.
- Sex chromosomes determine a person's gender at birth. Everyone inherits one sex chromosome from each parent. Mothers pass on only X chromosomes while fathers can pass on either an X or a Y chromosome.
- The chromosome passed on by the father then determines the sex of the offspring: females have two X chromosomes (XX), and males have one X chromosome and one Y chromosome (XY).
- Fabry disease affects mostly males, who receive one X chromosome with the abnormal gene.
- Females with Fabry disease also receive one X chromosome with the defective gene, however; since females have two X chromosomes, the normal X chromosome can offer some protection against developing the disorder.
- Fabry disease is caused by a genetic mutation resulting in a deficiency of an enzyme called alpha-galactosidase A (a-Gal A). The genetic defect causes the body to not make enough of this enzyme leading to a buildup of a type of fat called globotriaosylceramide (Gb3, or GL-3) in the body cause the symptoms of Fabry disease.
- Fabry disease is the result of what is called an X-linked inheritance, that is, the disease is caused by a defect on the X chromosome. X-linked genetic mutations tend to occur mostly in males and rarely in females.
- If a mother is carrying the defective gene for Fabry disease, both male and female children have a 50% chance of inheriting it from their mother. If the father is carrying the Fabry gene, the female children will inherit the defective gene because the father passes along an X chromosome to them, but the male children, who get a Y chromosome, will not.
- Females who inherit a defective X chromosome are called carriers and they may pass the genetic mutation on to their male children.
What are the symptoms of Fabry disease?
Signs and symptoms include:
- Episodes of pain and burning sensations in the hands and feet (acroparesthesias) that can be triggered by exercise, stress, fatigue, fever, or changes in weather
- Small, dark red spots on the skin (angiokeratomas), mostly in clusters from the belly button to the knees
- Decreased ability to sweat
- Cloudiness of the front part of the eye
- Problems with the gastrointestinal system
- Ringing in the ears (tinnitus)
- Hearing loss
- Mitral valve prolapse
- Abdominal discomfort
- Frequent bowel movements after eating
- Joint pain
- Back pain in the kidney area
How is Fabry disease diagnosed?
Fabry disease can be difficult to diagnose because it is so rare. The standard test to diagnose Fabry disease is a measurement of leukocyte alpha-Gal A enzyme activity. This test can detect the presence of the mutation for Fabry disease in males, however, it will only identify about 50% of the female carriers.
What is the treatment for Fabry disease?
Fabry disease may be treated using enzyme replacement therapy with agalsidase-alpha or agalsidase beta to help normalize kidney function, heart function, and blood supply to the brain.
Other treatments for Fabry disease are aimed at relieving individual symptoms.
- phenytoin, carbamazepine, or gabapentin may help prevent episodes of pain and burning sensations (acroparesthesias). Opioids may be prescribed for severe pain.
- Antiplatelet drugs such as aspirin, ticlopidine, clopidogrel, and aspirin-dipyridamole are prescribed to prevent recurrent ischemic strokes.
- Warfarin may be prescribed to prevent cardioembolic strokes.
- In severe Fabry disease that has progressed to kidney failure, hemodialysis and kidney transplantation may be necessary.
- Pancrelipase, metoclopramide, H2 blockers, such as cimetidine, famotidine, and others, and loperamide can help and soothe relieve gastrointestinal symptoms.
- ACE inhibitors and/or blockers are prescribed for high levels of protein in the urine (proteinuria) due to kidney damage.
- Hearing loss may be treated with hearing aids.
- Patients with high blood pressure (hypertension) may be prescribed antihypertensive medications and they should keep blood pressure under control.
- High cholesterol should also be treated.
- In addition to medications, patients should eat a balanced diet, exercise, and avoid smoking.
Because Fabry disease can affect many different organs many specialists may be consulted:
- Nephrologist for kidney problems
- Cardiologist for heart problems
- Neurologist or neurosurgeon for brain and nervous system symptoms
- Ophthalmologist for eye problems
- Gastroenterologist for digestive problems
- Otolaryngologist (ear, nose, and throat specialist, or ENT) for hearing problems
- Additionally, patients may benefit from working with physical therapists, nutritionists, and psychologists to help manage symptoms.
Patients may also wish to consult with genetic counselors.
What is the prognosis with Fabry disease?
The life expectancy of males with Fabry disease is about 58 years, and the life expectancy of females with Fabry disease is just over 75 years. The most common cause of death in both genders is cardiovascular disease.
Fabry Disease. NIH. 2019.
Fabry disease. NIH. Updated Jun 28, 2016.
Waldek, S. P., et al. "Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry." Genet Med. 2009 Nov;11(11):790-6. doi: 10.1097/GIM.0b013e3181bb05bb
Top Fabry's Disease Related Articles
Heart Healthy Diet: 25 Foods You Should EatWhat foods are heart healthy? Learn what foods help protect your cardiovascular system from heart attack, coronary heart disease, stroke, and cardiovascular disease. Plus, find easy meal recipes and menu ideas for more everyday heart benefit.
FeverAlthough a fever technically is any body temperature above the normal of 98.6 F (37 C), in practice, a person is usually not considered to have a significant fever until the temperature is above 100.4 F (38 C). Fever is part of the body's own disease-fighting arsenal; rising body temperatures apparently are capable of killing off many disease-producing organisms.
Back Pain QuizThere are numerous causes of chronic lower back pain and only one ailment gets more complaints. What is it? Quiz your knowledge of symptoms, treatments, problems, and reasons for common back pain.
DialysisDialysis is a procedure that performs many of the normal duties of the kidneys, like filtering waste products from the blood, when the kidneys no longer work adequately. There are two types of dialysis: Hemodialysis uses a filter to remove waste products and water from the body; and peritoneal dialysis removes excess waste and fluid with a fluid that is placed into the patient's stomach cavity through a special plastic tube.
Genetic DiseasesThe definition of a genetic disease is a disorder or condition caused by abnormalities in a person's genome. Some types of genetic inheritance include single inheritance, including cystic fibrosis, sickle cell anemia, Marfan syndrome, and hemochromatosis. Other types of genetic diseases include multifactorial inheritance. Still other types of genetic diseases include chromosome abnormalities (for example, Turner syndrome, and Klinefelter syndrome), and mitochondrial inheritance (for example, epilepsy and dementia).
Heart Detail PictureThe heart is composed of specialized cardiac muscle, and it is four-chambered, with a right atrium and ventricle, and an anatomically separate left atrium and ventricle. See a picture of Heart Detail and learn more about the health topic.
Heart Disease: Warning Signs of Cardiovascular Disease
Heart disease (coronary artery disease) occurs when plaque builds up in the coronary arteries, the vessels that supply blood to the heart. Heart disease can lead to heart attack. Risk factors for heart disease include:
- High blood pressure
- High cholesterol
- Family history
Angina, shortness of breath, and sweating are just a few symptoms that may indicate a heart attack. Treatment of heart disease involves control of heart disease risk factors through lifestyle changes, medications, and/or stenting or bypass surgery. Heart disease can be prevented by controlling heart disease risk factors.
CAD SlideshowWhat is heart disease (coronary artery disease)? Learn about the causes of heart disease, arrhythmias and myopathy. Symptoms of heart disease include chest pain and shortness of breath. Explore heart disease diagnosis, treatment, and prevention.
Heart Disease: Causes of a Heart AttackHeart disease prevention includes controlling risk factors like diet, exercise, and stress. Heart disease symptoms in women may differ from men. Use a heart disease risk calculator to determine your heart attack risk.
Heart Disease QuizTake our Heart Disease Quiz to get answers and facts about high cholesterol, atherosclerosis prevention, and the causes, symptoms, treatments, testing, and procedures for medically broken hearts.
Am I Having a Heart Attack? Symptoms of Heart DiseaseHeart attacks symptoms vary greatly for men and women, from anxiety and fatigue to nausea and sweating. Learn the warning signs of a heart attack and know the symptoms that may require an immediate trip to the hospital.
Kidney (Renal) Failure
Kidney failure can occur from an acute event or a chronic condition or disease. Prerenal kidney failure is caused by blood loss, dehydration, or medication. Some of the renal causes of kidney failure include sepsis, medications, rhabdomyolysis, multiple myeloma, and acute glomerulonephritis.
Post renal causes of kidney failure include bladder obstruction, prostate problems, tumors, or kidney stones.Treatment options included diet, medications, or dialysis.
Lower Back Pain (Lumbar Spine Pain)There are many causes of back pain. Pain in the low back can relate to the bony lumbar spine, discs between the vertebrae, ligaments around the spine and discs, spinal cord and nerves, muscles of the low back, internal organs of the pelvis, and abdomen, and the skin covering the lumbar area.
Peripheral NeuropathyPeripheral neuropathy is a problem with the functioning of the nerves outside of the spinal cord. Symptoms may include numbness, weakness, burning pain (especially at night), and loss of reflexes. Possible causes may include carpel tunnel syndrome, shingles, vitamin or nutritional deficiencies, and illnesses like diabetes, syphilis, AIDS, and kidney failure. Peripheral neuropathy is diagnosed with exams and tests. Treatment for the condition depends on the cause. Usually, the prognosis for peripheral neuropathy is good if the cause can be successfully treated or prevented.
Skin RashThe word "rash" means an outbreak of red bumps on the body. The way people use this term, "a rash" can refer to many different skin conditions. The most common of these are scaly patches of skin and red, itchy bumps or patches all over the place.
StrokeA stroke is an interruption of the blood supply to part of the brain caused by either a blood clot (ischemic) or bleeding (hemorrhagic). Symptoms of a stroke may include weakness, numbness, double vision or vision loss, confusion, vertigo, difficulty speaking, or understanding speech. A physical exam, imaging tests, neurological exam, and blood tests may be used to diagnose a stroke. Treatment may include administration of clot-busting drugs, supportive care, and in some instances, neurosurgery. The risk of stroke can be reduced by controlling high blood pressure, high cholesterol, diabetes, and stopping smoking.
Tinnitus is described as a throbbing, ringing, clicking, or buzzing in one or both ears. Tinnitus is caused by trauma to the ear, over exposure to loud noises, medication, and diseases or infections of the ear such as multiple sclerosis, TMJ, autistic neruoma, Meniere's disease, hearing loss, and aging. Treatments include medication, tinnitus masking, retraining therapy, and relief therapy.