What is Fabry disease?

Fabry disease (FD) is a rare, inherited disease. It’s progressive and can be life-threatening. People with FD have a damaged gene that leads to a shortage of an essential enzyme. The shortage results in a buildup of specific proteins in the body’s cells, causing damage to the:

  • heart
  • lungs
  • kidneys
  • skin
  • brain
  • stomach

The disease affects both men and women in all ethnic groups, but men are usually more severely affected.

There are two types of FD. Type 1 FD, also known as classic FD, starts in childhood and is less common than type 2, which has a later onset. An estimated 1 out of 117,000 people has FD.

FD is named for Johannes Fabry, a doctor in Germany who first described its symptoms in 1898. It’s also known as Anderson-Fabry disease, for William Anderson, a British doctor who also noted it in that same year. Other names for FD are:

  • galactosidase alpha (GLA) gene deficiency
  • enzyme alpha-galactosidase A deficiency
  • angiokeratoma corporis diffusum
  • angiokeratoma diffuse
  • ceramide trihexosidase deficiency

FD has many different symptoms, making diagnosis difficult. Symptoms can vary between men and women, and between type 1 and type 2 FD.

Symptoms of type 1 FD

Early symptoms of type 1 FD include:

  • Burning or tingling pain in the hands and feet. In males this can occur as early as 2 to 8 years old. In females it occurs later in childhood or adolescence. Episodes of intense pain, which can last from minutes to days, are called “Fabry crises.”
  • Lack of sweat production. This affects more males than females.
  • Skin rash. This reddish-purple rash is slightly raised and occurs between the belly button and the knees. It’s called angiokeratoma.
  • Stomach problems. This includes cramps, gas, and diarrhea.
  • Abnormal corneas. Blood vessels in the eyes may have a changed appearance, but this doesn’t affect vision.
  • General tiredness, dizziness, headache, nausea, and heat intolerance. Males may have swelling in their feet and legs.

As type 1 FD progresses, symptoms become more serious. When people with type 1 reach their 30s and 40s, they can develop kidney disease, heart disease, and stroke.

Symptoms of type 2 FD

People with type 2 FD also develop problems in these areas, although usually later in life, in their 30s to 60s.

Serious FD symptoms vary from person to person and can include:

  • A progressive decrease in kidney function, advancing to kidney failure.
  • Heart enlargement, angina (heart-related chest pain), irregular heartbeat, thickening of the heart muscle, and eventually heart failure.
  • Strokes, occurring in some men and women with FD in their 40s. This may be more common in women with FD.
  • Stomach problems. About 50-60 percent of women with FD may have pain and diarrhea.

Other signs of FD include:

Who inherits FD

A specific gene mutation causes FD. You inherit the damaged gene from your parents. The damaged gene is located on the X chromosome, one of the two chromosomes that determine your sex. Males have one X chromosome and one Y chromosome, and females have two X chromosomes.

A man with the FD gene mutation on the X chromosome will always pass it on to his daughters, but not to his sons. The sons get the Y chromosome, which doesn’t have the damaged gene.

A woman with the FD mutation on one X chromosome has a 50 percent chance of passing it on to her sons and daughters. If her son gets the X chromosome with the FD mutation, he will inherit FD.

Because a daughter has two X chromosomes, she may have less severe FD symptoms. This is because not all of her body’s cells will activate the X chromosome that carries the defect. Whether or not the damaged X chromosome is activated occurs early in your development and remains that way for the rest of your life.

How genetic mutations lead to FD

FD is caused by as many as 370 mutations in the GLA gene. Particular mutations tend to run in families.

The GLA gene controls the production of a particular enzyme called alpha-galactosidase A. This enzyme is responsible for breaking down a molecule in the cells known as globotriaosylceramide (GL-3).

When the GLA gene is damaged, the enzyme that breaks GL-3 down can’t function properly. As a result, GL-3 builds up in the body’s cells. Over time, this fatty buildup damages the cell walls of blood vessels in the:

  • skin
  • nervous system
  • heart
  • kidneys

The degree of damage FD causes depends on how severe the mutation in the GLA gene is. That’s why FD symptoms can vary from person to person.

FD can be difficult to diagnose because the symptoms are similar to those of other diseases. Symptoms are often present long before a diagnosis. Many people are not diagnosed until they have an FD crisis.

Type 1 FD is most often diagnosed by doctors on the basis of the child’s symptoms. In adults, FD is often diagnosed when they’re being tested or treated for heart or kidney problems.

An FD diagnosis for males can be confirmed by a blood test that measures the amount of the damaged enzyme. For females, this test isn’t sufficient, because the damaged enzyme may seem normal even though some organs are damaged. A genetic test for the defective GLA gene is necessary to confirm whether a female has FD.

For families with a known history of FD, prenatal tests can be performed to determine if a baby has FD.

Early diagnosis is important. FD is a progressive disease, which means that symptoms get worse over time. Early treatment can help.

FD can cause a wide variety of symptoms. If you have FD, you’ll probably see specialists for some of these symptoms. In general, treatment will aim at managing symptoms, relieving pain, and preventing further damage.

Once you’ve been diagnosed with FD, it’s important to regularly see your doctor to monitor your symptoms. People with FD are advised not to smoke.

Here are some FD treatment options:

Enzyme-replacement therapy (ERT)

ERT is now a first-line treatment recommended for all people with FD. Agalsidase beta (Fabrazyme) has been used since 2003, when it was approved by the U.S. Food and Drug Administration. It’s given intravenously, or through an IV.

Pain management

Pain management can involve avoiding activities that might bring on symptoms, such as strenuous exercise or temperature changes. Your doctor may also prescribe medications such as diphenylhydantoin (Dilantin) or carbamazapine (Tegretol). These are taken daily for pain reduction and prevention of FD crises.

For your kidney

A low-protein, low-sodium diet may help if you have a mildly reduced kidney function. If your kidney function gets worse, you may need kidney dialysis. In dialysis, a machine is used to filter your blood three times a week or more, depending on what type of dialysis you’re on and how much you need. A kidney transplant may also be necessary.

As-needed treatments

Heart problems will be treated as they are for people without FD. Your doctor may prescribe medications to manage the condition. Your doctor may also prescribe treatments to reduce the risk of stroke. For stomach problems, your doctor may prescribe medication or a special diet.

One potential complication of FD is end-stage renal disease (ESRD). ESRD can be deadly if you aren’t treated with dialysis or a kidney transplant. Almost all males with FD develop ESRD. But only about 10 percent of females with FD develop ESRD.

For people who are treated to control ESRD, heart disease is a major cause of death.

FD can’t be cured, but it can be treated. Awareness of FD is increasing. ERT is a relatively new treatment that helps stabilize symptoms and lower the occurrence of FD crises. Research is ongoing for other treatment possibilities. Gene replacement therapy is in a clinical trial. Another approach in the research phase, called chaperone therapy, uses small molecules to stop the damaged enzyme.

Life expectancy for people with FD is lower than that of the general U.S. population. For males, it’s 58.2 years. For females, it’s 75.4 years.

A frequently overlooked FD complication is depression. It can be helpful to reach out to other people who understand. There are several organizations for people with FD which have resources that can help both people with FD and their families: