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Fabry Disease: Symptoms, Causes, Diagnosis and Treatment

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People who have Fabry disease don’t produce enough healthy versions of an enzyme (blood chemical) called alpha-galactosidase A (alpha-GAL). These enzymes prevent sphingolipids, a fat-like substance, from collecting in blood vessels and tissue.

Without functioning alpha-GAL enzymes, harmful levels of sphingolipids build up in blood vessels and tissues. Fabry disease affects the heart, kidneys, brain, central nervous system and skin. It is an inherited condition passed from parent to child. It’s sometimes called Anderson-Fabry disease.

Fabry disease

What are the types of Fabry disease?

The types of Fabry disease reflect a person’s age when symptoms first appear. Types include:

  • Classic type: Symptoms of classic Fabry disease appear during childhood or the teenage years. One hallmark disease symptom — a painful burning sensation in the hands and feet — may be noticeable as early as age two. Symptoms get progressively worse over time.
  • Late-onset/atypical type: People with late-onset Fabry disease don’t have symptoms until they’re in their 30s or older. The first indication of a problem may be kidney failure or heart disease.

How common is Fabry disease?

Approximately one out of every 40,000 males has classic Fabry disease. Late-onset or atypical Fabry disease is more common. It affects about one in every 1,500 to 4,000 males.

Experts aren’t sure how many females have Fabry disease. Some females don’t have symptoms or have mild, easy-to-dismiss symptoms, so the condition frequently goes undiagnosed in women.

What causes Fabry disease?

Children inherit a mutation (change) in the galactosidase alpha (GLA) gene on the X chromosome from a parent. The GLA gene produces the alpha-GAL enzyme that helps break down fatty substances (sphingolipids). People who inherit a defective GLA gene don’t produce enough alpha-GAL enzyme. As a result, fatty substances build up in blood vessels.

Who might get Fabry disease?

People with Fabry disease inherit a mutated gene on the X chromosome from a parent. Males inherit one X chromosome from their mothers. Females have two X chromosomes, one from each parent.

A parent can pass on the faulty gene that causes Fabry disease to a child in different ways:

  • Fathers pass their X chromosome with the faulty gene to all of their daughters. All of these daughters will have the gene mutation that causes Fabry disease. Sons aren’t at risk because males get the Y chromosome from their fathers (not the X chromosome).
  • Mothers have a 50% chance of passing their affected X chromosome to their daughters or sons. Some family members can have the gene mutation while others don’t.

What are the symptoms of Fabry disease?

Symptoms of Fabry disease vary depending on the type. Some symptoms are mild and might not appear until later in life. Males tend to have more severe symptoms than females. Fabry disease symptoms include:

  • Numbness, tingling, burning or pain in the hands or feet.
  • Extreme pain during physical activity.
  • Heat or cold intolerance.
  • Abnormal opacity of the eye (cornea), which does not change someone’s vision.
  • Dizziness.
  • Flu-like symptoms, including fatigue, fever and body aches.
  • Gastrointestinal problems, such as diarrhea, constipation and abdominal pain.
  • Hearing loss or ringing in ears (tinnitus).
  • High levels of protein in urine (proteinuria).
  • Raised red or purplish skin lesions (angiokeratoma) on your chest, back and in the genital area.
  • Sweating less (hypohidrosis) or not at all (anhidrosis).
  • Swelling (edema) in the legs, ankles or feet.

How is Fabry disease diagnosed?

Your healthcare provider may order tests to diagnose Fabry disease, including:

  • Enzyme assay: This test measures alpha-GAL enzymes in blood. Measurements of 1% or lower indicate disease. This test is most reliable for males and should not be used in females.
  • Genetic: Because females with Fabry disease can have normal levels of alpha-GAL enzymes, providers use genetic testing (DNA sequencing) to identify the GLA gene mutation.
  • Newborn screenings: Some states test newborns for Fabry disease and other lysosomal storage disorders. The enzyme test is included as part of routine newborn screenings.

How is Fabry disease managed or treated?

There isn’t a cure for Fabry disease. Medications for pain and stomach problems can ease symptoms. There are two treatments that may slow down the build up of the fatty substances with the goal to prevent heart problems, kidney disease and other life-threatening complications:

  • Enzyme replacement therapy: Every two weeks, you receive an intravenous (IV) infusion of lab-made agalsidase beta enzyme (Fabrazyme®). This replacement enzyme does the work of the missing alpha-GAL enzyme so that fatty substances don’t build up. You may receive an antihistamine and other medications before therapy to prevent an allergic reaction.
  • Oral chaperone therapy: Chaperones are small molecules that repair faulty alpha-GAL enzyme. The mended enzymes can then break down the fatty substance. With this therapy, you take a pill (migalastat [Galafold®]) every other day to stabilize the faulty alpha-GAL enzyme. Not everyone with Fabry disease can be treated with this medication. It depends on your specific genetic mutation in the GLA gene if you are eligible for this treatment.

Researchers are actively developing several new therapies using genetic engineering and stem cell technologies.

What are the complications of Fabry disease?

Years of build up of the fatty substance can damage blood vessels and lead to life-threatening problems, such as:

  • Heart problems, including arrhythmia, heart attacks, enlarged heart and heart failure.
  • Kidney failure.
  • Nerve damage (peripheral neuropathy).
  • Strokes, including transient ischemic attacks (TIA or ministrokes).

How can I prevent Fabry disease?

Fabry disease is inherited. If you carry the mutated gene that causes Fabry disease, talk to a genetic counselor. This specialist can explain the chances of passing the gene to your children and discuss options. For instance, a process called preimplantation genetic diagnosis (PGD) identifies embryos that don’t carry the mutated gene. Your doctor implants healthy embryos during in vitro fertilization (IVF). PGD ensures your child won’t have the mutated gene or get Fabry disease.

What is the prognosis (outlook) for people with Fabry disease?

Fabry disease is a progressive disease. Symptoms, and the risk of serious complications, worsen with age. People with Fabry disease have a higher risk of life-threatening problems that can shorten life expectancy. On average, males with classic Fabry disease tend to live to their late 50s. Females with the disease often live into their 70s. You may add years to your life by getting appropriate care for heart and kidney disease and taking steps to reduce strokes.

When should I call the doctor?

You should call your healthcare provider if you have Fabry disease and experience:

  • Chest pain, irregular heartbeat, shortness of breath or signs of heart attack.
  • Excessive swelling or fluid retention.
  • Extreme dizziness, vision problems or signs of stroke.
  • Hearing loss.
  • Severe abdominal pain or diarrhea.

What questions should I ask my doctor?

You may want to ask your healthcare provider:

  • How did I get Fabry disease?
  • What type of Fabry disease do I have?
  • What is the best treatment for me?
  • What are the treatment risks and side effects?
  • Are my family members at risk for developing Fabry disease? If so, should we get genetic testing?
  • What type of ongoing care do I need?
  • Should I look out for signs of complications?
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