Fabry Disease: Symptoms, Causes, Diagnosis, and Treatment

Fabry Disease is a rare genetic disorder that affects approximately 1 in 40,000 to 60,000 people worldwide. This condition, caused by mutations in the GLA gene, leads to the accumulation of a particular type of fat within the body’s cells.

Despite its low prevalence, Fabry Disease can have profound effects on various organs, making early detection and management crucial for patients’ well-being. Symptoms often manifest in childhood or adolescence and can include skin lesions, gastrointestinal issues, kidney dysfunction, and cardiovascular complications. Understanding the intricacies of Fabry Disease is vital for improving diagnosis, treatment, and ultimately, the quality of life for affected individuals.

What is Fabry Disease?

Fabry disease, a rare genetic condition, results from insufficient production of the enzyme alpha-galactosidase A (alpha-GAL). This enzyme breaks down sphingolipids, preventing their accumulation in blood vessels and tissues. 

It’s a type of lysosomal storage disorder, that impacts the heart, kidneys, brain, nervous system, and skin. Also known as Anderson-Fabry disease or alpha-galactosidase-A deficiency, it leads to harmful sphingolipid buildup without functional alpha-GAL enzymes.

What are the Types of Fabry Disease?

Fabry disease manifests in various forms based on symptom onset, which are:

• Classic Type:

  Symptoms emerge in childhood or teenage years. Notably, a burning sensation in hands and feet may appear as early as age 2, worsening gradually.

• Late-Onset/Atypical Type:

  Symptoms typically arise after 30s. Manifestations may include kidney failure or heart disease, serving as initial indicators of the condition.

What are the Symptoms of Fabry Disease?

Fabry Disease (FD) presents a variety of symptoms, posing challenges in diagnosis. Manifestations differ among genders and between type 1 and type 2 FD.

Symptoms of Type 1 FD

• Early signs include burning or tingling pain in extremities.
• Males may experience these sensations as early as 2 to 8 years old, while females typically develop them later.
• “Fabry crises” entail episodes of intense pain lasting from minutes to days.
• Males predominantly suffer from a lack of sweat production.
• A characteristic skin rash, angiokeratoma, occurs between the belly button and knees.
• Stomach issues like cramps, gas, and diarrhoea are common.
• Abnormal corneas might manifest, though without affecting vision.
• General symptoms encompass tiredness, dizziness, headache, nausea, and heat intolerance.
• Type 1 FD progression brings about serious complications like kidney and heart diseases by the 30s or 40s.

Symptoms of Type 2 FD 

Similar complications arise but typically later in life, between the 30s and 60s.

Some serious FD symptoms are:

• Progressive decline in kidney function leads to failure.
• Cardiac manifestations include enlargement, angina, irregular heartbeat, and eventual heart failure.
• Stroke risk increases, particularly in women with FD in their 40s.
• Stomach issues affect a significant portion of women with FD.
• Other indicators comprise hearing loss, ringing in the ears, lung disease, and exercise intolerance. Fever might also occur.

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What are the Causes of Fabry Disease?

Inheritance of Fabry Disease (FD)

• FD is caused by a specific gene mutation inherited from parents.
• The defective gene is located on the X chromosome, determining sex.
• Males inherit one X and one Y chromosome, while females inherit two X chromosomes.
• A man with the FD mutation passes it to daughters, not sons (the Y chromosome lacks the mutation).
• A woman with one mutated X chromosome has a 50% chance of passing FD to sons and daughters.
• Daughters may have milder symptoms due to X chromosome inactivation.

Genetic Mutations and FD Development

• FD results from up to 370 mutations in the GLA gene.
• These mutations often run in families.
• The GLA gene regulates alpha-galactosidase A production, essential for breaking down GL-3.
• Damage to the GLA gene impairs enzyme function, leading to GL-3 accumulation.
• Accumulation damages blood vessel walls in the skin, nervous system, heart, and kidneys.
• Symptom severity varies based on mutation severity.

What are the Complications of Fabry Disease?

Accumulation of the fatty substance over time can harm blood vessels, potentially resulting in severe health complications such as:

1. Cardiac issues like arrhythmia, heart attacks, enlarged heart, and heart failure.
2. Renal failure.
3. Peripheral neuropathy (nerve damage).
4. Strokes, including transient ischemic attacks (TIA or mini-strokes).

How is Fabry Disease Diagnosed?

Tests to diagnose Fabry disease that your healthcare provider may order include:

1. Enzyme Assay: This test evaluates the activity of the alpha-GAL enzyme in your blood. A measurement of 1% or lower indicates the presence of the disease. However, it is important to note that this test is primarily reliable for men and individuals assigned male at birth (AMAB), rather than women and those assigned female at birth (AFAB).
2. Genetic Testing: Given that individuals with Fabry disease, particularly women and those AFAB, may have normal levels of alpha-GAL enzyme activity, healthcare providers often resort to genetic testing (DNA sequencing) to pinpoint mutations in the GLA gene.
3. Newborn Screenings: Newborns sometimes undergo screenings for Fabry disease and other lysosomal storage disorders as part of routine procedures.

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What is the Treatment for Fabry Disease?

Fabry disease, unfortunately, lacks a cure, but certain medications can alleviate pain and stomach issues associated with it. However, two treatments show promise in slowing down the accumulation of fatty substances, aiming to avert severe complications like heart and kidney problems:

Enzyme Replacement Therapy (ERT)

• Intravenous infusions of lab-made enzymes (agalsidase beta, pegunigalsidase alfa) mimic the missing alpha-GAL enzyme.
• These infusions, typically biweekly, prevent the buildup of fatty substances.
• Pre-treatment with antihistamines and other medications helps prevent allergic reactions.
• Infusions can be administered at infusion centres or at home.

Oral Chaperone Therapy

• Migalastat pills every other day repair faulty alpha-GAL enzymes, aiding in the breakdown of fatty substances.
• The particular genetic mutation in the GLA gene determines eligibility.

Ongoing research explores additional therapies utilising genetic engineering and stem cell technologies.

Conclusion

Fabry disease presents complex challenges, yet advancements in diagnosis, treatment, and support offer hope. Increased awareness and research are crucial for improving patient outcomes and quality of life. It is always advisable to seek medical help from an experienced neurologist. Timely care and help can ensure an appropriate diagnosis and treatment of your condition. 

At the CK Birla Hospital, we ensure patients get holistic medical support which includes treatment in a compassionate environment. This patient-centric approach not only helps patients heal better but also ensures they are aware of the preventive measures as well. In case you need to consult a neurologist, reach out to us, or book a direct appointment at the CK Birla Hospital.

FAQs

Can Fabry Disease Skip Generations?

Fabry disease can appear to skip generations due to the inheritance pattern. It is an X-linked genetic disorder, so males typically show symptoms while females can be carriers.

Can Females have symptoms of Fabry disease?

Females can have symptoms of Fabry disease if they inherit the mutated gene from both parents or if they inherit one mutated gene and have skewed X-chromosome inactivation.

Is Fabry Disease Fatal?

Fabry disease can lead to serious complications affecting multiple organs and may reduce life expectancy, but with appropriate management, including enzyme replacement therapy, life expectancy can be improved.

Can Fabry Disease be Prevented?

Fabry disease cannot be prevented as it is a genetic disorder caused by mutations in the GLA gene. However, genetic counselling and testing can help in family planning and management.

Are There Any Dietary Restrictions for Individuals With Fabry Disease?

There are generally no specific dietary restrictions for individuals with Fabry disease, but maintaining a healthy diet low in saturated fats and sodium may help manage associated complications like kidney disease.

Can Fabry Disease Lead to Complications During Pregnancy?

Fabry disease can potentially lead to complications during pregnancy, such as worsening of symptoms due to increased physiological demands, but each case varies and requires careful management by healthcare professionals.