Understanding Fabry Disease: Types, Risks, and Emerging Therapies

Fabry disease is a rare inherited genetic disorder that affects your body’s ability to produce a special enzyme that breaks down certain fats. As a result, fat builds up in your tissues and blood vessels. Over time, this can harm your kidneys, heart, and nervous system. If left untreated, Fabry disease can be life-threatening. Fortunately, with proper treatment, you can manage symptoms and lead a healthier life. 

What Is Fabry Disease?

Fabry disease is part of a group of illnesses known as lysosomal storage diseases. It is a genetic disease that you get from your parents. In this disease, you lack an important enzyme called alpha-galactosidase A (α-GAL A). This enzyme helps break down a fatty substance called globotriaosylceramide (GL-3). Therefore, when this enzyme is missing or not working properly, GL-3 builds up in your blood vessels, kidneys, heart, skin, and brain. This leads to symptoms like pain, skin problems, stroke, and even kidney or heart failure [1].

Fabry disease results from a mutation (change) in a gene on the X chromosome. As men have only one X chromosome, they are primarily affected. Females have two X chromosomes, so they have milder symptoms or no symptoms at all. This is because if one X chromosome is affected, the other compensates. But, in some cases, women can also have severe symptoms.

The symptoms of Fabry disease usually worsen over time. If you do not get proper treatment, you may experience severe complications like kidney failure, heart disease, or even early death. This is why you need early diagnosis and proper treatment.

Types of Fabry Disease

According to the age at which you first experience symptoms, Fabry disease is divided into two types. They are given below [2][3]:

Classic Fabry Disease (Type 1): The classic Fabry disease is the more severe type, but it is less common. The symptoms appear in childhood or adolescence. Some patients even experience symptoms as early as age 2. It progresses faster and can cause symptoms like burning pain in hands and feet, skin rashes, stomach problems, and slow growth.

Late-onset Fabry Disease (Type 2): This is a milder and more common form of the disease. The symptoms of this disease appear in adulthood, usually after the age of 30. Unlike the classic type, it doesn’t cause early symptoms like pain or skin problems. Instead, it mainly causes heart and kidney problems. 

What Causes Fabry Disease?

Fabry disease is a genetic disorder caused by a mutation in the GLA gene located on the X chromosome [1]. This gene tells your body to produce an enzyme called alpha-galactosidase A. If you have this disease, your body can’t produce enough healthy (properly shaped) versions of this enzyme. This enzyme is responsible for breaking down a fatty substance called globotriaosylceramide. A lack of this enzyme causes fatty substances to build up in your blood vessels and organs like the heart, kidneys, and nervous system. 

The disease is passed down from parents to children. Fathers pass their X chromosome to all their daughters. Therefore, all daughters will carry the faulty gene. However, sons are not affected because males get their X chromosome from their mother. On the other hand, mothers have a 50% chance of passing their faulty gene for Fabry disease to their sons or daughters [4].

Signs and Symptoms

The symptoms of Fabry disease vary from person to person depending on the patient’s age, sex, and disease type. The symptoms usually get worse over time. Normally, males have more severe symptoms while females have milder ones. Here are some common symptoms seen at different ages [1][5][6]:

Symptoms in Childhood and Teenage Years

The following symptoms of Fabry disease are seen in children and teenagers:

• Burning pain in the hands and feet (often the first symptom)
• Clusters of small, dark red spots on the skin
• Decreased ability to sweat
• Cloudy vision
• Stomach pain, bloating, diarrhea

Symptoms in Adulthood

Over time, as the disease progresses, it can cause more severe symptoms, including:

Kidney Problems: You can have kidney problems, like protein or blood in your urine. Over time, this can lead to kidney failure. In case of kidney failure, you will need dialysis or a kidney transplant.

Heart Problems: Fabry disease can lead to heart problems like thickening of the heart muscles, irregular heartbeat, heart attacks, heart failure, etc.

Hearing Problems: You may experience hearing loss or ringing in the ears (tinnitus).

Neurological Problems: Over time, the disease damages the blood vessels in your brain. This leads to symptoms like weakness, dizziness, stroke, chronic fatigue, etc.

Please note that these symptoms significantly increase your risk of premature death if left untreated.

Diagnosis

The diagnosis of Fabry disease is difficult because it is a rare condition, and its symptoms mimic many common conditions. However, early diagnosis and proper treatment are crucial for effectively managing this condition. Here are some steps doctors take to diagnose this disease [1][5]:

Review of Medical History and Symptoms: At first, your doctor will ask about your past medical history and current symptoms. If they suspect Fabry disease, they will recommend some diagnostic tests to confirm.

Blood Test: In males, doctors usually measure the activity of the alpha-galactosidase A enzyme through a blood test. Low levels of activity of this enzyme confirm the diagnosis. However, this test is ineffective in females, as many of them have a normal level of this enzyme.

Genetic Test: This is the most reliable way to confirm Fabry disease, especially for females. It checks for mutations in the GLA gene. 

Imaging and Organ Testing: Depending on the symptoms, your doctor might recommend MRI tests, kidney tests, and heart tests to check for organ damage.

Note: If one member of a family is diagnosed with this disease, it is necessary to run tests on other members as well, since the disease is inherited.

Treatment

Currently, there is no cure for Fabry disease. However, there are several treatment options available to manage the symptoms and slow the disease’s progression. Currently, there are two drug treatments available for this disease [1][4][5]. They are given below:

Enzyme Replacement Therapy (ERT): This is the standard treatment of Fabry disease. You will receive a synthetic version of the missing enzyme (alpha-galactosidase A) via intravenous infusion. This therapy helps clear the fat that builds up in your blood vessels and organs. As a result, it can relieve symptoms like pain and slow the progression of kidney and heart damage. 

Oral Chaperone Therapy: This is a newer treatment option for people over 16 years who have specific types of Fabry disease. It works by stabilizing and properly shaping the faulty enzyme so that it can function better in the body.

Fabry disease normally affects your entire body and damages organs. That’s why your doctor might suggest some additional treatments to manage your symptoms. Here are some of the additional treatments:

• Pain medications to relieve nerve pain.
• If you have heart problems, then depending on the severity, your doctor might suggest surgery, medications, or a pacemaker.
• Medicines for stomach problems like bloating or diarrhea.
• For kidney problems, your doctor might suggest ACE inhibitors. In case of kidney failure, doctors will recommend dialysis or a kidney transplant.

As of July 2025, some promising new treatments are currently in development, like gene therapy [1][7]. Gene therapy has the potential to fully cure the disease as it can replace the faulty gene in your body responsible for this disease. Other potential therapies include substrate reduction therapy, RNA-based treatments, etc. 

FAQs

Here are some frequently asked questions about Fabry Disease:

1. How common is Fabry disease?

Fabry disease is a rare condition. The exact prevalence of this disease varies depending on the type of disease, a person’s sex, ethnicity, and geographic location. The classic form is less common and mostly affects males. It is estimated to occur in about 1 in every 22,000 to 40,000 males. On the other hand, the late-onset Fabry disease is more common. It affects about 1 in every 1000 to 3000 males and 1 in every 6000 to 40,000 females [8].

2. Does Fabry disease affect life expectancy?

Yes. Fabry disease is a progressive disorder, and it gets worse over time. It can reduce life expectancy, especially in males. On average, males with classic Fabry disease may live into their 50s, while women can live into their 70s [9]. However, early diagnosis and proper treatment can greatly improve your survival and quality of life.

 3. Can people with Fabry disease have children?

Yes. People with this disease can have children, but they should seek genetic counseling. A genetic specialist can figure out the risk of passing the condition to your children and explain the options available to you. One such option is a process called PGD (preimplantation genetic diagnosis), which can ensure that your child will not have the disease.