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What is Fabry Disease
Fabry disease is a rare genetic disorder. A gene defect (mutation) alters a protein, called an enzyme, that normally breaks down a particular fat (globotriaosylceramide).
The mutation keeps the enzyme from breaking down the fat. This causes excess fat to build up in the blood vessels (vasculature) of many organs of the body. Over time, this results in less blood flow and fewer nutrients getting to the body’s organs. The buildup can also wear away at nerve fibers.
Fabry disease is a systemic, X-linked, lysosomal storage disorder that results from the deficient activity of the enzyme α-galactosidase A (α-Gal A) and the lysosomal accumulation of its primary glycolipid substrate, globotriaosylceramide (GL-3). The progressive GL-3 accumulation, particularly in vascular endothelial lysosomes, leads to ischemia and occlusion of small vessels throughout the body. Clinical onset in affected males with the Type 1 Classic phenotype occurs in childhood or adolescence and is characterized by painful acroparesthesias, gastrointestinal dysfunction, corneal dystrophy, absent or decreased sweat (anhidrosis or hypohidrosis), and cutaneous lesions (angiokeratomas). With advancing age, the progressive glycolipid accumulation, especially in podocytes and cardiomyocytes, leads to kidney failure, cardiac disease, ischemic strokes, and early demise. Patients typically develop end-stage kidney disease (ESKD) in the third to fifth decades of life. Female heterozygotes from Type 1 Classically affected families can be as severely affected as Type 1 Classically affected males, or may be asymptomatic throughout life, primarily as a result of random X-chromosomal inactivation. Patients with the Type 2 Later-Onset phenotype lack the childhood manifestations of the Type 1 Classic early-onset phenotype and often are unrecognized.
Previously undiagnosed males with both Types 1 and 2 Fabry disease have been identified in hemodialysis, cardiac, and stroke clinics by screening patients for markedly deficient plasma α-Gal A activity. Such studies have identified that ∼0.2% of males on hemodialysis have unrecognized Fabry disease. Since the disease is X-linked, at-risk family members should be screened, and affected patients should receive genetic counseling, medical evaluations, and early therapeutic intervention, especially in males with the Type 1 Classic phenotype.
That causes pain and other symptoms. The areas most often affected are the hands, feet, skin, eyes, and digestive system. Eventually the fatty deposits can affect your cardiovascular system, nervous system, and kidneys. This can cause a heart attack, stroke, kidney damage, or other life-threatening complications.
What are the causes?
Fabry disease is caused by a genetic mutation. This mutation is passed down through families (inherited).
What increases the risk?
You may be more likely to have Fabry disease if:
- You are male.
- You have a family history of the disease.
What are the symptoms of Fabry disease?
Symptoms of Fabry disease include:
- A rash of small, raised, reddish-purple dots on the skin (angiokeratomas).
- Cloudy eyes or other eye problems.
- Chronic pain, especially in the hands or feet.
- Burning sensations in the hands and feet.
- Gastrointestinal problems, such as bloating, diarrhea, and frequent bowel movements.
- Ringing in the ears (tinnitus).
- Hearing loss.
- Decreased sweat production (hypohidrosis) or no sweat production (anhidrosis).
Over time, untreated Fabry disease can cause:
- Severe back pain in the area of the kidneys.
- Heart attack.
- Stroke.
How is this diagnosed?
Your health care provider may suspect Fabry disease based on your symptoms and family history. Your health care provider will also perform a physical exam. This may include tests, such as:
- A blood test to measure enzyme activity in your blood (enzyme assay).
- A blood test to look for mutations in the gene that causes Fabry disease.
- Urine tests to check how well your kidneys are working and to check for protein in your urine.
- An ultrasound of your heart (echocardiogram) to create an image of your heart and check for heart disease.
If you or your partner has Fabry disease and you are having a child, your child can be screened for the condition at birth. If the results of that test are out of the normal range, the child may need follow-up blood and urine tests. These would help confirm the diagnosis and help determine treatment. Prenatal testing for Fabry disease also can be done.
How is this treated?
Medicines are used to manage Fabry disease. This may include:
- Enzyme replacement therapy. This medicine performs the functions of the enzyme that is missing in Fabry disease.
- Medicines to treat the pain and discomfort in your hands and feet.
You may also need treatment for complications caused by Fabry Disease. These complications may be related to your kidneys or heart. Treatments may include:
- Angioplasty to repair or unblock an artery.
- Heart surgery.
- Dialysis to filter your kidneys.
- Kidney transplant.
Follow these instructions at home:
- Avoid stressful situations when possible. Stress can worsen the pain related to Fabry disease.
- Stay indoors when the temperatures are very hot or very cold.
- Exercise carefully, as directed by your health care provider. Physical exertion can make Fabry disease worse.
- Practice good hygiene to avoid illnesses that make Fabry disease worse.
- Have a good support system in place.
Contact a health care provider if:
- You have worsening pain.
- You have worsening vision.
- You have a noticeable decrease in urination.
- You have swelling of your hands, feet, or lower legs that is getting worse.
- You feel increasingly weak or tired.
Get help right away if:
- You have trouble breathing, chest pain, or a feeling of pressure in your chest.
- You have stroke symptoms. These include:
- Numbness or weakness on one side of your body.
- Droopiness on one side of your face.
- Slurred speech.
- Confusion.
- You have sharp pain in the area of your kidneys.
5 Interesting Facts of Fabry disease
1. Patients undergoing hemodialysis may have unrecognized Fabry disease, a treatable X-linked kidney disease. The plasma α-galactosidase A (α-Gal A) assay reliably diagnoses affected males but not heterozygous females, who require mutation analysis for accurate diagnosis.
2. Enzyme replacement therapy in Fabry disease can clear the kidney glycolipid accumulation and stabilize kidney function; early treatment and adequate dose (1 mg/kg every other week) are important.
3. Females in families with X-linked Fabry disease can develop proteinuria and kidney failure.
4. The differential diagnosis of postpartum proteinuria should include Fabry disease.
5. Males undergoing hemodialysis can be screened for Fabry disease by identifying those with deficient plasma α-Gal A activity, and then confirming the diagnosis by mutation analyses. At-risk family members can then be diagnosed for genetic counseling, medical evaluations, and early therapeutic intervention.
