Fabry disease is a genetic disorder that can damage your nerves and major organs, including your kidneys. Though rare, Fabry disease can affect several members of a single family. In a recent presentation by the American Kidney Fund, Dr. Michael Mauer, a pediatric nephrologist at the University of Minnesota, explained what Fabry disease is and how you can find out if it may be the cause of your kidney problems.*

What is Fabry disease?

Fabry disease results from a mutation in a gene, known as the GLA gene, on your X chromosome. The GLA gene provides instructions for making the alpha galactosidase A enzyme, which breaks down a fatty substance called globotriaosylceramide. The mutated gene prevents or reduces the production of alpha galactosidase A. Without this enzyme, globotriaosylceramide doesn’t break down and instead, the fatty substance accumulates in blood vessels and tissues throughout your body.

Fabry is heterogeneous, meaning that it affects people differently. Since males have only one X-chromosome, a mutated gene means that they will almost definitely get the disease, and most likely the severe, classic form of it. Females have two X-chromosomes, so a mutated gene may result in a milder form of the disease. In rare cases, a woman may not experience symptoms at all. Males with classic Fabry disease are at high risks of injury to vital organs.

What are the signs and symptoms of Fabry disease?

Signs and symptoms of Fabry disease usually manifest as:

• Pain in your hands and/or feet (acroparesthesias)
• Clusters of dark red or purple-raised spots on your skin (angiokeratomas) that may begin in adolescence or young adulthood 
• Cloudiness, whorls, or streaks in a spoke-like pattern on the front of the eye (corneal opacity or corneal verticillata) that do not impair vision 
• Heat intolerance and decreased ability to sweat (hypohidrosis)
• Gastrointestinal issues such as,
  • Abdominal pain
  • Diarrhea
  • Nausea
• Ringing in your ears (tinnitus)
• Hearing loss/deafness in one or both ears

What are some complications of Fabry disease?

As with its signs and symptoms, Fabry disease can also cause complications across multiple body systems and may include:

• Progressive kidney disease and kidney failure
• Reduced production of tears and saliva
• Blood clots, heart attack, or stroke
• Enlargement of the left side of your heart 
• Scarring of the heart muscle
• Irregular heart rhythm and heart valve abnormalities
• Anxiety, depression, and/or thoughts of suicide

How is Fabry disease diagnosed?

Fabry disease is diagnosed using a combination of:

• Visible symptoms, such as the aforementioned purplish rash and corneal verticillata 
• Physical symptoms, such as pain in your hands and feet and decreased saliva production
• Family history
• Age
• Enzyme activity
• DNA, kidney, or heart biopsy 

The disease may be diagnosed by a dermatologist, neurologist, nephrologist, ophthalmologist, or other specialist.

How is Fabry disease treated?

The disease is most often treated with enzyme replacement therapy (ERT). In the United States, this takes the form of agalsidase beta (brand name Fabrazyme), manufactured by Sanofi-Genzyme. The treatment is administered by intravenous infusion, usually every two weeks. There is also an oral therapy called migalastat (brand name Galafold), which is given in capsule form every other day. 

Several other treatments are being explored in clinical trials, including a plant-based ERT called Protolix, and several forms of gene therapy.

*American Kidney Fund. (2021, Apr. 21). The Link Between Fabry Disease and Your Kidneys [Video]. https://www.kidneyfund.org/training/webinars/the-link-between-fabry-disease-and-your-kidneys.html