Fabry disease is a rare genetic condition that belongs to a class of disorders known as lysosomal storage diseases. Named after Johannes Fabry who discovered it, the disease is inherited in an X-linked manner, meaning that the mutation responsible for it is located on that chromosome. Since men only have one X chromosome, the disease is more common in men than in women, who need two copies of the mutation to develop the condition. According to the "Dalili Medical" website, Fabry disease affects about 1 in 40,000 children, and the late forms of the disease are more common, and usually occur as a result of a deficiency in a certain enzyme, with symptoms appearing in childhood or adolescence.
. What are the signs of Fabry disease?
Signs of this disease include feeling pain in the hands and feet, a rash, in addition to kidney or heart problems.
. What causes Fabry disease?
This disease is caused by mutations in the GLA gene, which leads to the accumulation of a fatty substance in the cells.
. How is Fabry disease diagnosed?
Diagnosis includes genetic testing and measuring enzyme activity levels in the blood.
. What are the treatment options for Fabry disease?
Treatment options include enzyme replacement therapy as well as medications to control symptoms.
. What are the types of Fabry disease?
There are two main types: classic Fabry disease and late-onset Fabry disease, which differ in the age at which symptoms begin and the severity of symptoms.
What is Fabry disease?
Fabry disease (FD) is a rare, progressive, and potentially life-threatening genetic condition. People with the condition have a defect in a specific gene that results in a deficiency of a vital enzyme. This deficiency causes certain proteins to build up inside the body’s cells, damaging the following organs:
- Heart
- Lungs
- Kidneys
- Skin
- Brain
- Stomach
The disease can affect men and women of all races, but men are more often affected. There are two types of the disease: Type 1 (FD), also known as classic Fabry disease, which begins in childhood and is less common than type 2, which appears later. An estimated 1 in 117,000 people have Fabry disease. The disease is named after Johannes Fabry, the German physician who first described its symptoms in 1898. It is also known as Anderson-Fabry disease, after the British physician William Anderson who noted the condition in the same year.
**How common is Fabry disease?**
Fabry disease affects 1 in 40,000 men, making it a rare and serious condition. It is important to manage the disease early to avoid it getting worse later on.
**Is Fabry a genetic disease?**
Fabry disease is a genetic disorder caused by a mutation, or change, in a section of DNA. The defective gene is located on the X chromosome, one of the sex chromosomes. Sex chromosomes determine the sex of a child at birth, with each person inheriting one sex chromosome from each parent. Mothers only pass on the X chromosome, while fathers can pass on either the X or Y chromosome. Fabry disease mainly affects males, who inherit one X chromosome carrying the abnormal gene.
**Types of Fabry disease**
The types of Fabry disease vary based on the age of the person when symptoms first appear, and include the following types:
- **Classic type**: Symptoms of this type appear in childhood or the teenage years. The characteristic symptom is a burning pain in the hands and feet, which can begin as early as age 2, and then gradually worsen over time.
- **Late-onset atypical**: People with this type of Fabry disease do not have any symptoms until they are in their 30s or older. Kidney failure or heart disease is often the first sign of a health problem.
**Diagnosis**
Your doctor may order a series of tests to diagnose Fabry disease, including:
- **Enzyme test**: This test measures the level of alpha-gal enzymes in the blood. If the level is 1% or less, this is an indication of the disease. This test is most reliable for males, and is not recommended for females.
- **Genetic Test**: Because females with Fabry disease may have normal levels of alpha-gal enzymes, specialists rely on genetic testing (DNA sequencing) for the mutant GLA gene.
- **Newborn Screening**: Newborns are screened for Fabry disease and other genetic disorders associated with lysosomal dysfunction (lysosomal storage diseases). The enzyme test is part of routine newborn screening.
**Symptoms of Fabry Disease**
Fabry disease has a wide range of symptoms, making diagnosis difficult. Symptoms differ between men and women, as well as between types 1 and 2.
**Type 1 Symptoms:**
Early symptoms of type 1 include:
- **Burning or tingling pain:** Patients feel pain in the hands and feet. This pain can start in males as early as 2 to 8 years old, while in females it appears later during childhood or adolescence. Severe episodes of pain that can last from minutes to days are known as "Fabry crises."
- **Lack of sweating:** This condition affects males more than females.
- **Rash:** A slightly reddish-purple rash appears, and occurs between the belly button and the knees, and is known as a hemangioma.
- **Stomach problems:** These problems include cramps, gas, and diarrhea.
- **Changes in blood vessels:** The appearance of the blood vessels in the eye may change, but this does not affect vision.
- **Fatigue and dizziness:** Patients experience general fatigue, dizziness, headaches, nausea, and heat intolerance. Males may also experience swelling in their feet and legs.
As the disease progresses in type 1, symptoms become more severe. When patients reach their 30s andFor those in their 40s, they may experience more serious health problems.
**Type 2 Symptoms**
People with type 2 have problems in several areas, although these symptoms often appear later in life, between the 30s and 60s. Serious symptoms of Fabry disease vary from person to person, and may include:
- Gradual deterioration in kidney function, which can lead to kidney failure.
- Enlargement of the heart, angina (chest pain related to the heart), irregular heartbeat, thickening of the heart muscle, and eventually heart failure.
- Strokes occur in some men and women with diabetes in their 40s, as this condition may be more common in women with Fabry disease.
- Digestive problems, as about 50-60% of women with diabetes suffer from pain and diarrhea.
Other signs of the disease include:
- Hearing loss.
- Ringing in the ears.
- Lung disease.
- Intolerance to strenuous exercise.
- Fever.
**Complications of Fabry disease**
The accumulation of fat over the years can damage blood vessels, leading to serious, life-threatening health problems, such as:
- Heart problems, including irregular heartbeats, heart attacks, enlarged heart, and heart failure.
- Kidney failure.
- Nerve damage (peripheral neuropathy).
- Strokes, including transient ischemic attacks (TIA) or mini-strokes.
### Treatment options for Fabry disease
Fabry disease causes a variety of symptoms, and people with it may need to see specialists if they have chronic kidney disease. Treatment generally aims to control symptoms, relieve pain, and prevent damage from getting worse. Once diagnosed with Fabry disease, it becomes necessary to follow up with a doctor regularly to monitor symptoms. People with this disease are advised to avoid smoking. Here are some treatment options:
#### Enzyme replacement therapy (ERT)Enzyme replacement therapy (ERT) is the first line treatment recommended for people with Fabry disease. Agalsidase beta (Fabrazyme) has been used since 2003 after being approved by the FDA and is given intravenously.
#### Pain management Pain management may include avoiding activities that may worsen symptoms, such as strenuous exercise or sudden changes in temperature. Your doctor may also prescribe medications such as diphenylhydantoin (Dilantin) or carbamazepine (Tegretol) to take daily to reduce pain.
**Kidney treatment**A low-protein, low-sodium diet can be helpful for people with mildly impaired kidney function. As kidney function worsens, dialysis may be necessary. Dialysis involves using a machine to filter the blood three or more times a week, depending on the type of dialysis and the patient’s needs. In some cases, a kidney transplant may also be an option.
**Treatments as needed**Heart problems will be treated in the same way as people who don't have COPD. Your doctor may prescribe medications to control the condition, as well as treatments to reduce your risk of stroke. Your doctor may also recommend medications or a special diet to treat stomach problems.