Fabry Disease

Publication Details

What is Fabry?

Fabry is an inherited condition that causes deposits to build up in cells over time. Our bodies contain thousands of active substances called enzymes. For example, your stomach has enzymes that help break down the food you eat. Some of these enzymes are stored in structures called lysosomes, which help the body break down proteins, carbohydrates, and fatty substances.

In people without Fabry, the enzyme alpha-galactosidase A (pronounced al-fa-ga-lak-toe-sy-daze A), or alpha-GAL, breaks down a fatty acid called globotriaosylceramide (pronounced glow-bow-try-oh-sill-ser-ah-mide), or GL-3. People with Fabry do not have enough of the alpha-GAL enzyme. As a result, lysosomes fill up with GL-3 and no longer work normally. This is why Fabry disease is called a “lysosomal storage disorder”.

The build-up of GL-3 in the walls of blood vessels and other tissues can cause damage to major organ systems. The heart, kidneys, and brain may not function properly, causing problems that could be life-threatening.

How is Fabry passed on?

Fabry is an X-linked condition. This means that the gene that makes alpha-GAL is found on the X chromosome, one of the sex chromosomes. Males have one X and one Y, and females have two Xs. Males pass an X chromosome to their daughters and a Y chromosome to their sons. Women pass an X chromosome to all of their children, daughters and sons. Therefore, men with Fabry cannot pass it to their sons but will pass it to their daughters, and women with Fabry can pass it to both their sons and daughters.

Alex’s Story

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My name is Alex, and I have Fabry. No one on my dad’s side has Fabry, but lots of relatives on my mom’s side do.

My grandfather, Joe, had it. He was diagnosed in his early 50s and died soon after. We think his two brothers also had it (they both passed away in their 40s). Grandpa Joe passed the gene change to my mother and all her sisters, Sarah, Maggie, and Jane.

My mom passed the gene change to me, and Aunt Sarah passed it to my cousin, Katie. Aunt Maggie didn’t have any children, and Aunt Jane passed the Fabry gene change to two of her children, Nick and Megan.

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Who is at risk?

  • Fabry occurs in both men and women, but it often affects males more severely than females.
  • Fabry affects people of all races and ethnicities, all over the world.
  • Women with Fabry have a 50% chance of passing it to their children – both daughters and son – during each pregnancy.
  • Men with Fabry will pass it down to all of their daughters and none of their sons.

Major signs and symptoms

  • Fatigue
  • Burning pain in the extremities
  • Impaired sweating
  • Starburst pattern on the cornea (corneal whorling)
  • Skin rash, or angiokeratomas
  • Hearing problems
  • Gastrointestinal problems
  • Kidney problems
  • Heart problems
  • Stroke

The signs and symptoms of Fabry may appear in affected individuals at any age, and often appear later in females than in males. Family members with Fabry – even siblings – may have very different symptoms.

Diagnosis

It is important to know if you have Fabry disease, because Fabry can cause many health problems, including pain, heart problems, and kidney problems. Because Fabry disease is progressive, early diagnosis and access to appropriate medical care is especially important. However, Fabry is not very well known, and many people endure months and years of misdiagnosis before receiving a definitive diagnosis of Fabry. Many people experience symptoms of Fabry early in childhood – perhaps as early as four years old. Unfortunately, these early signs and symptoms are sometimes misunderstood, or even ignored, by parents, teachers, and other caregivers. This can lead to delays in seeking medical care as well as possible feelings of anger, self-doubt, depression, or even hopelessness at not being taken seriously (for more about these psychological reactions and others, see page 12).

Testing

Males with Fabry can be diagnosed through a simple test that indicates whether or not the enzyme alpha-GAL is present in the blood. Females, on the other hand, may have Fabry even if they have nearly normal levels of alpha-GAL. Therefore, genetic testing, which analyzes DNA, is needed to determine whether a female has Fabry. Genetic testing for Fabry involves a blood draw, and there are some psychological considerations. See page 10 for more on emotional and psychological issues.

If you are considering being tested for Fabry disease, genetic counselors can provide support before, during, and after your test.

Genetic counselors are specialized healthcare professionals with experience in medical genetics and counseling. They are trained to help individuals as they consider being tested, when the results are received, and in the weeks and months afterward.

Before testing, counselors can provide balanced information so you can make an informed decision about testing. They can also help both individuals and family members to be psychologically prepared to cope with a positive test.

If test results are positive, counselors can help the individual and the family adjust to the test results, and can assist them with understanding whatever specialist follow-up is necessary.