Common Signs of Fabry Disease and Treatment Options

What is Fabry Disease?

Fabry disease is a rare, inherited genetic disorder caused by mutations in the GLA gene, leading to a deficiency of an enzyme called alpha-galactosidase A. It causes damage to vital organs and systems over time. Because it affects multiple systems, Fabry disease can present a wide range of symptoms, often making it challenging to diagnose.

Common Signs and Symptoms of Fabry Disease

Fabry disease symptoms can manifest in childhood or adulthood and vary significantly among individuals, depending on the severity of the enzyme deficiency. Here are the most common signs to watch for:

1. Pain and Burning Sensations (Acroparesthesias)

Many patients experience intense episodes of burning pain, particularly in the hands and feet. These episodes can be triggered by stress, physical exertion or changes in temperature.

2. Skin Lesions (Angiokeratomas)

Small, dark red or purple spots may appear on the skin, particularly around the lower abdomen, thighs or buttocks. These lesions are a hallmark sign of Fabry disease.

3. Reduced Sweating (Hypohidrosis)

Many individuals with Fabry disease experience a decrease in their ability to sweat, making it difficult to regulate body temperature, especially during hot weather or physical activity.

4. Gastrointestinal Issues

Stomach pain, bloating, nausea and diarrhea are common, as the accumulation of GL-3 can affect the gastrointestinal system.

5. Kidney Problems

Kidney function often deteriorates over time due to the buildup of GL-3, leading to protein in the urine (proteinuria) and eventually kidney failure in severe cases.

6. Heart Complications

Fabry disease can lead to heart-related issues, including an enlarged heart (left ventricular hypertrophy), arrhythmias or even heart failure, as GL-3 accumulates in cardiac tissue.

7. Corneal Verticillata

An eye exam may reveal whorled patterns on the cornea, known as corneal verticillata, which usually do not affect vision but are indicative of Fabry disease.

8. Hearing Loss or Tinnitus

Hearing loss and ringing in the ears (tinnitus) can occur due to vascular or nerve involvement.

9. Fatigue

Many individuals report chronic fatigue, which can stem from the combined effects of systemic symptoms, organ dysfunction and pain.

10. Stroke or Transient Ischemic Attacks (TIAs)

Young adults with Fabry disease may experience strokes or mini-strokes, often before the condition is diagnosed, due to vascular abnormalities.

Treatment Options for Fabry Disease

While there is no cure for Fabry disease, significant advances in treatment have improved the quality of life for patients. The primary goals of treatment are to manage symptoms, slow disease progression and prevent organ damage.

1. Galafold (Migalastat)

Galafold is the first and only oral treatment approved for adults with Fabry disease who have specific genetic mutations. It works as a chaperone therapy, stabilizing the faulty alpha-galactosidase A enzyme, allowing it to function more effectively and reduce GL-3 buildup.

Benefits of Galafold include:

  • Convenient oral administration (no infusions required).
  • Reduces GL-3 accumulation in cells.
  • Improves organ function and quality of life in eligible patients.

2. Enzyme Replacement Therapy (ERT)

For patients who are not eligible for Galafold, enzyme replacement therapy remains the cornerstone of treatment. ERT involves intravenous infusions of the missing enzyme to break down GL-3 in cells.

Two commonly used ERTs are:

  • Fabrazyme (Agalsidase Beta).
  • Replagal (Agalsidase Alfa).

ERT can slow disease progression and alleviate symptoms but requires lifelong infusions.

3. Pain Management

Medications like gabapentin or pregabalin are often prescribed to manage neuropathic pain associated with Fabry disease. Pain episodes may also require lifestyle adjustments, such as avoiding temperature extremes.

4. Supportive Therapies

  • Kidney support. Dialysis or kidney transplantation may be necessary in cases of severe kidney failure.
  • Cardiac care. Pacemakers or medications to manage arrhythmias and heart failure.
  • Gastrointestinal management. Dietary changes and medications to manage nausea, diarrhea, or bloating.

5. Gene Therapy (Emerging Option)

Research is ongoing into gene therapy approaches to correct the underlying genetic mutation and provide a long-term solution for Fabry disease. These treatments are still in experimental stages but offer hope for future breakthroughs.

Living with Fabry Disease

Early diagnosis and a comprehensive treatment plan are crucial for managing Fabry disease. Genetic testing can confirm the diagnosis, and family members may also benefit from screening due to its hereditary nature.

In addition to medical treatments, patients can improve their quality of life by:

  • Following a healthy, balanced diet.
  • Staying hydrated and managing heat exposure.
  • Joining support groups for emotional and social support.

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