This rare inherited disease cannot be cured but can be treated. Researchers continue to work to understand Fabry disease and find new treatment options.
Fabry disease (FD) is a rare inherited disease. It’s progressive and can be life threatening. FD is the result of a damaged gene that leads to a shortage of an essential enzyme. The shortage results in a buildup of specific proteins in your cells, which can damage the following organs:
- heart
- lungs
- kidneys
- skin
- brain
- stomach
The disease can occur in people from all ethnic groups. It usually affects males more severely than females.
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
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 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
Because FD has many symptoms, it can be difficult to diagnose. Symptoms can vary between males and females 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 your 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. You may also experience Fabry crises, which are episodes of intense pain that can last from minutes to days.
- Lack of sweat production: This affects more males than females.
- Skin rash: A slightly raised, reddish-purple rash called angiokeratoma may appear between your belly button and your knees.
- Stomach problems: Cramps, gas, and diarrhea may occur.
- Atypical corneas: Blood vessels in your eyes may have an unusual appearance, but this will not affect your 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 may develop symptoms in similar areas to those with type 1, but symptoms usually occur later in life, when people are in their 30s to 60s.
Serious FD symptoms vary from person to person and can include:
- a progressive decrease in kidney function, leading to kidney failure
- heart enlargement, angina (heart-related chest pain), irregular heartbeat, thickening of the heart muscle, and eventually heart failure
- strokes, which can occur in some people with FD in their 40s and may be more common in females with FD
- stomach problems such as pain and diarrhea, which may occur in
50% to 60% of females with FD
Other symptoms of FD include:
- hearing loss
- ringing in your ears
- lung disease
- intolerance of strenuous exercise
- fever
A specific gene mutation (change) 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.
Who inherits FD
A male who has the FD gene mutation on the X chromosome will pass it to his daughters but not to his sons. The sons get the Y chromosome, which does not have the damaged gene.
A female who has the FD mutation on one X chromosome has a 50% chance of passing it to any of her children. If her son gets the X chromosome with the FD mutation, he will inherit FD.
Because a daughter receives 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 mutation. The damaged X chromosome may become activated early in development and will remain that way for the rest of the child’s life.
How genetic mutations lead to FD
FD is caused by more than 370 mutations in the GLA gene. Particular mutations tend to run in families.
The GLA gene controls the production of an enzyme called alpha-galactosidase A. This enzyme is responsible for breaking down a molecule called globotriaosylceramide (GL-3) in your cells.
When the GLA gene is damaged, the enzyme that breaks down GL-3 cannot work properly. As a result, GL-3 builds up in your cells. Over time, this fatty buildup damages the cell walls of blood vessels in the following areas:
- 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 is made. Many people do not receive a diagnosis until they have an FD crisis.
Doctors most often diagnose type 1 FD on the basis of a child’s symptoms. In adults, doctors often diagnose FD during testing or treatment for heart or kidney problems.
In males, doctors can confirm an FD diagnosis with a blood test that measures the amount of the damaged enzyme. For females, this test is not enough, because the damaged enzyme may seem normal even though some organs are damaged. A genetic test for the GLA gene mutation is necessary to confirm whether a female has FD.
When people who have a known family history of FD are expecting a child, prenatal tests can determine whether a baby has FD.
Early diagnosis is important. FD is a progressive disease, which means the symptoms get worse over time. Early treatment can help.
FD can cause a wide variety of symptoms. If you have FD, you’ll probably work with specialists to treat some of these symptoms. In general, treatment will aim to manage symptoms, relieve pain, and prevent further damage.
Once you’ve received an FD diagnosis, it’s important to visit your doctor regularly to monitor your symptoms. Doctors will also typically recommend that you not smoke.
Here are some FD treatment options:
Enzyme-replacement therapy (ERT)
ERT is now a first-line treatment recommended to all people with FD. Agalsidase beta (Fabrazyme) has been used since 2003, when it was approved by the Food and Drug Administration (FDA). It’s given intravenously (directly into your vein).
Pain management
Pain management can involve avoiding triggers that might cause symptoms, such as strenuous exercise and temperature changes. A doctor may also prescribe medications such as phenytoin (Dilantin) or carbamazepine (Tegretol). You may take these daily to help reduce pain and help prevent FD crises.
Kidney function
A low protein, low sodium diet may help if you have a mildly reduced kidney function.
If your kidney function worsens, you may need kidney dialysis. This treatment involves using a machine to filter your blood three times per week or more, depending on which type of dialysis you’re receiving and how much you need.
A kidney transplant may also be necessary.
As-needed treatments
Heart problems will be treated the same way they are in people without FD. A doctor may prescribe medications to manage your condition and to reduce the risk of stroke.
For stomach problems, your doctor may prescribe medication or a special diet.
One possible complication of FD is end stage renal disease (ESRD). ESRD can be deadly if it’s not treated with dialysis or a kidney transplant. Almost all males with FD develop ESRD, but only about
Heart disease is a major cause of death in people who receive treatment to manage ESRD.
FD cannot be cured, but it can be treated. Awareness of the disease is increasing. ERT is a relatively new treatment that helps stabilize symptoms and reduce the occurrence of FD crises.
Research into other possible treatments is ongoing. Gene replacement therapy is in a clinical trial. Another approach that’s in the research phase, called chaperone therapy, involves using small molecules to stop the damaged enzyme.
The life expectancy for people with FD is lower than that of the overall U.S. population: 20 years lower for males and 10 years lower for females.
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 that offer resources for people with the disease and their families: