Fabry Disease

Updated November 22, 2019

Latest Revision: November 22, 2019

Author and Contributing Experts to this Guide include:

Jessica Bucher Genetic Counselor, MSGC LinkedIn

What Is Fabry Disease?

Fabry disease is a genetic condition that results from the build up of a particular type of fat, called globotriaosylceramide (GL-3), in the body's cells.

 It is considered a lysosomal storage disorder because people affected by Fabry have lysosomes (part of the cell that holds enzymes) that cannot break down GL-3. Buildup of this fat can cause symptoms that affect many parts of the body.

What's in this Guide?

Disclaimer: Before You Read

It is important to know that your genes are not your destiny. There are various environmental and genetic factors working together to shape you. No matter your genetic makeup, maintain ideal blood pressure and glucose levels, avoid harmful alcohol intake, exercise regularly, get regular sleep. And for goodness sake, don't smoke.

Genetics is a quickly changing topic.

Fabry can cause episodes of pain, skin spots, worsening kidney damage, heart attack, and stroke.

Causes of Fabry Disease 

Fabry disease is caused by mutations in the GLA gene, which provides instructions for making an enzyme called alpha-galactosidase A.

This enzyme breaks down GL-3. Mutations in the GLA gene cause the enzyme to be missing or not work properly, allowing the build up of GL-3 in cells throughout the body 1.

The Genetic Pattern of Inheritance of Fabry Disease 

Fabry disease is inherited in an X-linked manner 2. This is because the GLA gene is located on the X chromosome.

Males have one X chromosome and one Y chromosome. Because females have two copies of the X chromosome, one altered copy of the gene in each cell usually leads to less severe symptoms in females than in males, or rarely may cause no symptoms at all.

The chance of inheriting the GLA alteration for Fabry disease depends on whether it came from the father or the mother. For each pregnancy, a woman with Fabry disease has a 50% chance (1 in 2) of passing on the GLA alteration to her son or daughter.

However, a father with Fabry disease will always pass on the GLA alteration to his daughter. On the other hand, the father will never pass on the GLA alteration to any of his sons, since sons always get their X chromosome from their mother.

What Population Is Affected By Fabry Disease? 

It is estimated that about 1 in 50,000 males are affected by Fabry disease. Based on the size of the U.S. populations that comes out to be over 3,000 males in the U.S.

The condition also occurs in females, but the fabry disease prevalence is unknown. Milder, late-onset forms of the disorder are probably more common than the classic, severe form.

Recognize The Signs And Symptoms Of Fabry Disease 

Signs of Fabry include 3:

  • Episodes of pain, particularly in hands and feet
  • Small, dark red spots on skin (angiokeratomas)
  • Reduced or absent sweating (hypohidrosis or anhidrosis) 
  • Gastrointestinal symptoms like stomach pain, nausea, and vomiting
  • Ringing in the ears (tinnitus), and hearing loss
  • Cloudiness of the front part of the eye (corneal opacity)

Fabry disease symptoms in females can be as severe as those in males, but are usually milder. Some females with a known GLA alteration may not develop any symptoms 4.

Complications Associated with Fabry Disease 

Fabry disease also involves potentially life-threatening complications such as:

  • Worsening kidney damage
  • Heart attack
  • Stroke

Some affected individuals have milder forms of the disorder that appear later in life and affect only the heart or kidneys.

A Diagnosis of Fabry Disease

The diagnosis of Fabry disease can be made with two different tests:

For males:

  • Enzyme test: A blood test can measure the level of an enzyme called alpha-galactosidase A. Males with classic Fabry disease essentially have no alpha-galactosidase A enzyme (less than 1% of normal). Males with a non-classic Fabry gene mutation will have some enzyme but it is still very low. 
  • DNA test: Analysis of the GLA gene looking for a mutation

For females, a DNA test of the GLA gene is required. This is because the enzyme levels may be low or near-normal in females. DNA tests can be performed using blood or saliva.

What Age Is Fabry Disease Diagnosed? 

In a study based upon the Fabry Registry, due to the nonspecific nature of early symptoms in Fabry disease, diagnostic delays and misdiagnosis were common.

For males, the median age of symptom onset is 9 years, but the median age of diagnosis is not until 24 years. For females, the median age of onset is 13 years, but the median age of diagnosis is 31 years. However, there are many people of both sexes that may get diagnosed much later in life. 

Are There Prenatal Test For Fabry Disease? 

Prenatal testing for Fabry disease is possible if there is a known GLA gene variant in an affected family member. This is usually done via chorionic villus sampling or amniocentesis. 

Your Treatment and Care Options for Fabry Disease 

Currently there are two medications approved by the Federal Food and Drug Administration (FDA) for the treatment of Fabry disease in the United States 5: an enzyme replacement therapy (ERT) and a chaperone therapy.

The FDA approved enzyme replacement therapy (ERT) treatment for Fabry disease in the United States is called Fabrazyme 6, or agalsidase beta.

The goal of ERT is to replace the enzyme missing in individuals with Fabry disease, so that their body can breakdown GL-3 and prevent it from being stored in cells within the body.

Patients getting ERT usually receive the enzyme every other week by an intravenous infusion. Replacing the enzyme helps slow the progression of the disease, reduces complications, and may even prevent long-term complications.

The FDA approved chaperone therapy for Fabry disease in the United States is called Galafold, or migalastat. It works by stabilizing the body's own dysfunctional enzyme, so that it can work better.

Migalastat is a pill that is taken by mouth every day. This medication can only be used for people that have one of the specific mutations that have been shown to respond to this drug. Therefore, a DNA test of the GLA  gene is needed before potentially starting this medication. 

There are also other treatments that may help with some of the symptoms of Fabry disease. There are certain medications that may help alleviate some of the nerve pain associated with this disease. Other medications may be used to help protect the kidneys from damage.

There is no specific fabry disease diet that may help with symptoms. But some people with Fabry find that eating small meals. taking probiotics, and avoiding spicy, lactose-containing, or greasy foods also help decrease GI issues.

Is There A Cure For Fabry Disease? 

Currently, there is no known cure for Fabry disease. However, there is a gene therapy approach in the experimental stages that might one day lead to a cure.

Gene therapy for Fabry disease is designed to introduce a healthy copy of the GLA gene to restore normal levels of the alpha-galactosidase A enzyme.

Prognosis for Fabry Disease 

The life expectancy of males with Fabry disease was 58.2 years, compared with 74.7 years in the general population of the United States.

The life expectancy of females with Fabry disease was 75.4 years, compared with 80.0 years in the United States general population. However, therapies such as ERT may improve life expectancy. 

What to do Next: Living with Fabry Disease 

The National Fabry Disease Foundation (NFDF) is an organization dedicated to supporting the Fabry disease community and is a great resource for patients and families affected with this condition.

Referenced Sources

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  2. Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry.
    Wilcox WR1, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, Sims K, Waldek S, Pastores GM, Lee P, Eng CM, Marodi L, Stanford KE, Breunig F, Wanner C, Warnock DG, Lemay RM, Germain DP; Fabry Registry. 2008 Feb;93(2):112-28. Epub 2007 Nov 26.
  3. Fabry.
    Baby's First Test. Retrieved online. 2019.
  4. Fabry disease.
    U.S. National Library of Medicine. Genetics Home Reference. Reviewed: February 2012, Published: November 12, 2019.
  5. Fabry disease.
    Emory University - Department of Human Genetics in collaboration with ThinkGenetic. DATE UPDATED: 2019-01-22.
  6. Experimental Treatments for Fabry Disease.
    Fabry Disease News. Retrieved online. 2019.