If you’re seeking to understand Fabry disease, you’ve come to the right place. This rare genetic condition can be complex, but this guide breaks it down into clear, easy-to-understand sections. We will cover what Fabry disease is, its causes, the common symptoms, and how it is diagnosed and managed.

What Is Fabry Disease?

Fabry disease is a rare, inherited disorder that affects many parts of the body, including the skin, kidneys, heart, and nervous system. It belongs to a group of conditions known as lysosomal storage diseases.

To understand this, think of your body’s cells as tiny factories. Inside these factories are recycling centers called lysosomes. Lysosomes use special tools, called enzymes, to break down waste materials. In Fabry disease, a specific enzyme called alpha-galactosidase A (alpha-GAL) is either missing or doesn’t work correctly.

Without a functioning alpha-GAL enzyme, a fatty substance called globotriaosylceramide (often shortened to GL-3 or Gb3) builds up inside the cells. Over time, this buildup causes damage to cells and tissues throughout the body, leading to the wide range of symptoms associated with the disease.

The Genetic Cause of Fabry Disease

Fabry disease is caused by a mutation, or flaw, in the GLA gene. This gene contains the instructions for making the alpha-GAL enzyme. The GLA gene is located on the X chromosome, one of the two chromosomes that determine a person’s sex. This is why Fabry disease is called an X-linked disorder.

Because of this inheritance pattern, the disease affects males and females differently:

  • Males: Males have one X chromosome and one Y chromosome (XY). If they inherit a faulty GLA gene on their X chromosome, they will typically develop the classic, more severe form of the disease because they have no other X chromosome with a working copy of the gene to compensate.

  • Females: Females have two X chromosomes (XX). If they inherit a faulty GLA gene on one X chromosome, they still have a normal copy on their other X chromosome. This normal copy can often produce some functional alpha-GAL enzyme. For this reason, women with Fabry disease can have symptoms that range from very mild to just as severe as those seen in men.

A father with Fabry disease cannot pass it to his sons, but he will pass the faulty gene to all of his daughters. A mother with the faulty gene has a 50% chance of passing it to each of her children, regardless of their sex.

Common Signs and Symptoms

The symptoms of Fabry disease can vary greatly from person to person and often appear during childhood or adolescence. They tend to worsen over time as more GL-3 accumulates in the body’s cells.

Early Symptoms

  • Pain Crises: One of the most common early signs is episodes of severe, burning pain in the hands and feet. This is known as acroparesthesia. These pain crises can be triggered by stress, fatigue, fever, or exercise.

  • Skin Lesions: Many people with Fabry disease develop small, dark red or purplish spots on their skin called angiokeratomas. They often appear in clusters between the belly button and the knees but can be found elsewhere.

  • Reduced Sweating: A decreased ability to sweat, called hypohidrosis, is common. This can lead to overheating and an intolerance to heat and exercise. In some cases, people may not be able to sweat at all (anhidrosis).

  • Gastrointestinal Problems: Frequent digestive issues are common, including abdominal pain, cramping, diarrhea, and nausea, especially after eating.

  • Corneal Whorl: A doctor can often see a cloudy or streaky pattern in the cornea of the eye during an eye exam. This is called a corneal whorl or cornea verticillata. It does not typically affect vision but is a strong indicator of the disease.

Later-Stage Complications

As the disease progresses, the buildup of GL-3 can cause serious damage to major organs.

  • Kidney Disease: The kidneys are particularly vulnerable. Progressive damage can lead to kidney failure, requiring dialysis or a kidney transplant. Protein in the urine is often an early sign of kidney involvement.

  • Heart Problems: The heart muscle can become thickened (cardiomyopathy), and heart rhythm problems (arrhythmias) can develop. This increases the risk of heart attack, heart failure, and other cardiovascular complications.

  • Nervous System Issues: The accumulation of GL-3 in blood vessels that supply the brain can increase the risk of stroke or transient ischemic attacks (TIAs), even at a young age. Hearing loss and ringing in the ears (tinnitus) are also common.

Diagnosis and Testing

Diagnosing Fabry disease involves a few key steps. A doctor may suspect the condition based on a patient’s symptoms and family history.

  1. Enzyme Assay: This is a blood test that measures the activity level of the alpha-GAL enzyme. In males, a very low or absent level of enzyme activity confirms the diagnosis of classic Fabry disease. However, this test is not always reliable for females, as their enzyme levels can sometimes appear within the normal range even if they have the disease.

  2. Genetic Testing: A definitive diagnosis for all patients, especially females, is made through genetic testing. This blood test analyzes the GLA gene to identify the specific mutation that is causing the disease.

Once a diagnosis is confirmed, doctors will often recommend additional tests to check for organ damage, such as kidney function tests, an echocardiogram to look at the heart, and an MRI of the brain.

Treatment and Management Strategies

While there is no cure for Fabry disease, there are effective treatments that can help manage symptoms, slow the progression of the disease, and improve quality of life.

Disease-Specific Therapies

  • Enzyme Replacement Therapy (ERT): This is the primary treatment for many patients. ERT involves regular intravenous (IV) infusions of a manufactured version of the missing alpha-GAL enzyme. This helps the body break down the excess GL-3. The two main ERT drugs available are agalsidase beta (brand name: Fabrazyme) and agalsidase alfa (brand name: Replagal, available in some countries).

  • Chaperone Therapy: This is a newer, oral medication. The main drug in this class is migalastat (brand name: Galafold). It works differently from ERT. It acts as a “chaperone” that helps the patient’s own faulty alpha-GAL enzyme fold correctly so it can function better. This therapy is only effective for people with certain types of GLA gene mutations.

Symptom Management

In addition to disease-specific therapies, managing individual symptoms is crucial. This may include:

  • Medications to control nerve pain, such as gabapentin or carbamazepine.

  • Drugs like ACE inhibitors or ARBs to protect the kidneys.

  • Medications to manage heart conditions and prevent blood clots.

  • Lifestyle adjustments, such as avoiding extreme temperatures and staying hydrated.

Early diagnosis and consistent treatment are key to achieving the best possible long-term outcomes for individuals living with Fabry disease.

Frequently Asked Questions

  1. Is Fabry disease contagious? No, Fabry disease is not contagious. It is a genetic disorder that is passed down from parents to their children through genes. You cannot catch it from another person.

  2. Can women have severe symptoms of Fabry disease? Yes. While it was once believed that women were only “carriers” who did not experience symptoms, it is now understood that women can have a wide range of symptoms, from mild to severe. Because females have two X chromosomes, the severity often depends on which X chromosome is active in different cells of the body, a random process called X-inactivation.

  3. How common is Fabry disease? Fabry disease is considered a rare disease. Estimates suggest it affects approximately 1 in every 40,000 to 60,000 males. The prevalence in females is harder to determine but is thought to be higher.