What is Fabry Disease, and how does it affect those who have it? Fabry Disease, also known as Anderson-Fabry Disease, is a rare genetic disorder that falls under the category of lysosomal storage diseases. It’s important to understand the signs of Fabry disease so you can identify and manage this disease effectively.
What is Fabry Disease?
This condition is caused by the deficiency of an enzyme called alpha-galactosidase A, which leads to the accumulation of a specific type of fat, known as globotriaosylceramide (GL-3 or Gb3), in various cells and tissues throughout the body. This accumulation can cause a wide range of symptoms and complications, affecting multiple organ systems.
Symptoms
The symptoms of Fabry Disease can vary widely among individuals, even within the same family. The disease typically manifests in childhood or adolescence, but some symptoms may not appear until adulthood.
Common Symptoms
- Pain: One of the earliest and most common symptoms is pain, often described as burning or tingling, in the hands and feet (acroparesthesia). Pain episodes can be triggered by exercise, fatigue, stress, or temperature changes.
- Skin Lesions: Small, dark red spots called angiokeratomas can appear on the skin, particularly in the area between the belly button and knees.
- Decreased Sweating: Many individuals with Fabry Disease experience hypohidrosis (reduced ability to sweat), which can lead to heat intolerance.
- Gastrointestinal Issues: Abdominal pain, nausea, vomiting, and diarrhea are common due to the accumulation of GL-3 in the gastrointestinal tract.
- Ocular Issues: Corneal verticillata, a whorl-like pattern on the cornea, is often seen in patients but typically does not affect vision. Other eye issues can include cataracts and conjunctival vessel tortuosity.
- Cardiac Complications: These may include left ventricular hypertrophy (thickening of the heart muscle), arrhythmias, and heart valve abnormalities.
- Kidney Problems: Proteinuria (protein in the urine) is a common early sign of kidney involvement, which can progress to chronic kidney disease and eventually renal failure if untreated.
- Neurological Issues: Strokes or transient ischemic attacks (TIAs) can occur due to vascular complications.
Causes
Fabry Disease is caused by mutations in the GLA gene, which provides instructions for making the enzyme alpha-galactosidase A. This enzyme is essential for the breakdown of globotriaosylceramide (GL-3 or Gb3) or lipids. When there is a deficiency or absence of this enzyme, GL-3 accumulates in various cells and tissues, leading to the symptoms and complications associated with the disease.
Fabry Disease is inherited in an X-linked manner, meaning the defective gene is located on the X chromosome. Males, who have only one X chromosome, are typically more severely affected. Females, who have two X chromosomes, can also be affected but often have milder symptoms.
Treatments
While there is no cure for Fabry Disease, several treatment options can help manage symptoms, prevent complications, and improve quality of life.
- Enzyme Replacement Therapy (ERT): ERT involves regular infusions of a synthetic version of the alpha-galactosidase A enzyme. This treatment helps reduce the accumulation of GL-3 in cells, alleviating symptoms and slowing disease progression. Two ERTs commonly used are agalsidase beta (Fabrazyme) and agalsidase alfa (Replagal).
- Chaperone Therapy: This treatment involves small molecules that stabilize the dysfunctional enzyme, enhancing its activity. Migalastat (Galafold) is an oral chaperone therapy approved for use in patients with amenable GLA mutations.
- Pain Management: Medications such as anticonvulsants, antidepressants, and nonsteroidal anti-inflammatory drugs (NSAIDs) can help manage pain associated with Fabry Disease.
- Kidney Protection: Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are often prescribed to manage proteinuria and protect kidney function.
- Cardiac Care: Patients may require medications to manage heart issues, such as beta-blockers, ACE inhibitors, or anti-arrhythmic drugs. In some cases, pacemakers or implantable cardioverter-defibrillators (ICDs) may be necessary.
- Lifestyle Adjustments: Patients are often advised to avoid triggers that can exacerbate symptoms, such as extreme temperatures, strenuous exercise, and dehydration. Regular follow-up with a multidisciplinary team of specialists is crucial to monitor and manage the various aspects of the disease.
- Gene Therapy: Although still in the experimental stage, gene therapy holds promise as a potential future treatment for Fabry Disease. This approach aims to correct the underlying genetic defect and restore normal enzyme function.
Early diagnosis and prompt initiation of treatment are critical in managing Fabry Disease effectively. With appropriate care, individuals with Fabry Disease can lead relatively normal lives and reduce the risk of severe complications.