Fabry Disease: A Rare Genetic Disorder Explained Simply
February 1, 2025

Fabry disease or Fabry syndrome is a rare genetic illness caused by a malfunction with the enzyme alpha-galactosidase. The other name for this condition is Anderson Fabry disease. This enzyme is essential for breaking down certain lipids in the body. When insufficient or absent, these lipids accumulate in the bloodstream and tissues, causing long-term harm.
The illness can start in childhood and affect numerous sections of the body. Typical symptoms include hand and foot pain, red or purple spots on the skin, decreased sweating, blurry eyesight, gastrointestinal problems, tinnitus, and hearing loss. If untreated, it can cause severe complications like heart attacks, strokes, and kidney failure.
Available treatments include enzyme replacement therapy and oral medications, which can assist in managing symptoms and preventing complications.
Types of Fabry Disease
There are two forms of Fabry disease based on when symptoms start to show: congenital or late onset.
Classical: The classic type typically begins in childhood or adolescence. One of the earliest signs of this condition is a burning pain in the hands and feet, which can even be noticeable by the age of two. As time goes on, other symptoms may also emerge, leading to a decline in various areas of the body.
Late-onset: The late-onset form, often referred to as atypical Fabry disease, does not show symptoms until adulthood, sometimes appearing in the 30s or later. Severe health conditions such as kidney failure or heart disease often appear as the first signs, while affected individuals may not notice any issues in their younger years.
Symptoms of Fabry Disease
Fabry disease symptoms can differ significantly from person to person, with men generally experiencing more severe effects than women. These symptoms may emerge in childhood but often become more noticeable with age. Common signs of Fabry disease include:
- Neurological Symptoms: Numbness, tingling, burning sensations, or chronic pain in the hands and feet, which can intensify during physical activity.
- Temperature Sensitivity: Difficulty tolerating extreme heat or cold.
- Skin Changes: Dark red or purple raised skin lesions (angiokeratomas) that commonly appear on the chest, back, and groin.
- Eye Abnormalities: A distinctive corneal pattern (cornea verticillata), which does not affect vision but is visible during an eye exam.
- Hearing and Balance Issues: Hearing loss, ringing in the ears (tinnitus), and dizziness.
- Gastrointestinal Problems: Episodes of diarrhea, constipation, and abdominal pain.
- Kidney and Heart Complications: Protein in the urine (proteinuria), swelling in the legs and feet (edema), and an increased risk of high blood pressure, heart disease, and kidney failure.
- Reduced Sweating: A decreased ability to sweat (hypohidrosis) or complete absence of sweating (anhidrosis).
- General Fatigue and Flu-like Symptoms: Persistent tiredness, fever, and body aches.
Because Fabry disease tends to worsen over time, identifying it early and implementing appropriate treatment is vital to reducing the risk of serious health complications.
Causes
A mutation in the GLA gene causes Fabry disease by disrupting the production of alpha-galactosidase A (alpha-GAL), an essential enzyme. This enzyme is found in lysosomes and is responsible for breaking down globotriaosylceramide, a type of fatty substance. When the GLA gene is defective, the enzyme may be missing or not work properly, leading to a buildup of fatty substances in cells throughout the body. This buildup occurs in blood vessels, kidneys, heart, and nervous system cells, resulting in the symptoms associated with Fabry disease.
The severity of Fabry’s disease varies based on how much enzyme activity is affected. If there is a complete loss of enzyme activity, the individual experiences the classic, more severe form of the disease, which typically appears in childhood. In cases where enzyme activity is only partially reduced, individuals may develop late-onset forms that are milder and usually present in adulthood, often affecting specific organs like the heart, kidneys, or brain.
Who Is at Risk of Developing Fabry Disease?
Fabry disease is a hereditary disorder resulting from a mutation in the GLA gene found on the X chromosome. Since biological males (AMAB) have only one X chromosome, inheriting a mutated copy of the gene means they will develop the condition. Biological females (AFAB), who have two X chromosomes, may have milder symptoms or, in some cases, may not experience any symptoms at all.
The inheritance pattern of Fabry disease depends on which parent carries the mutated gene:
- If the father has Fabry disease, all of his daughters will inherit the altered gene, while his sons will not be affected, as they inherit the Y chromosome.
- If the mother has Fabry disease, there is a 50% chance that she will pass the mutated gene to each child, regardless of sex.
While some individuals with the gene mutation may show no signs, many—especially males—develop significant symptoms over time.
Diagnosis of Fabrys Diseases
Several tests are performed to diagnose Fabry disease:
- Enzyme Assay is a blood test that assesses the activity of the alpha-GAL enzyme. A significant indicator of Fabry disease is very low enzyme activity (1% or less). This test is primarily reliable for men and those assigned male at birth.
- Genetic testing is also conducted to detect mutations in the GLA gene, as enzyme levels can be normal in women and individuals assigned female at birth.
In many regions, newborns are routinely screened for Fabry disease along with other lysosomal storage disorders.
Treatment and Management
Although a cure for Fabry disease has not yet been found, there are treatments available that can alleviate symptoms, slow the disease’s advancement, and lower the likelihood of complications like heart and kidney issues.
Enzyme Replacement Therapy (ERT) or Oral Chaperone Therapy can be used to either provide synthetic enzymes that mimic the missing ALpha- Gal enzymes or help heal the existing weaker ones.
Additionally, medications aimed at alleviating symptoms, such as pain relievers and treatments for gastrointestinal issues, can enhance the overall quality of life.
Conclusion
Fabry disease is a rare genetic condition, and its significance lies in the fact that early diagnosis and appropriate treatment can substantially improve the quality of life and overall prognosis. While there is no cure, enzyme replacement therapy and oral chaperone therapy provide hope by addressing the underlying issues and slowing the progression of the disease. Raising awareness of the symptoms, particularly in families with a history of Fabry disease, is essential for ensuring timely treatment. Individuals with Fabry disease can enjoy more fulfilling lives by staying informed and collaborating with their healthcare providers.
Frequently Asked Questions
1. Can you prevent Fabry disease?
Since Fabry disease is inherited, it cannot be prevented. However, if you carry the mutated gene, it’s important to consult with a genetic counselor. They can help you understand the likelihood of passing the gene to your children and explore available options. One such option is preimplantation genetic diagnosis (PGD), a technique that screens embryos for the gene mutation. During in vitro fertilization (IVF), only embryos without the mutation are selected for implantation, reducing the risk of passing on Fabry disease.