Fabry disease is an inherited disorder in which the body does not produce enough of an enzyme called alpha-galactosidase A. It can affect various systems of the body. It is one of 50 lysosomal storage disorders. These disorders disrupt the normal activity of the lysosome, which contains enzymes necessary for breaking down and recycling different molecules in human cells.
Inherited
When a child diagnoses with Fabry disease, a parent should test to see if they have the same mutation in the GLA gene. If both parents are unaffected, the child is likely to have inherited the disease from one of their parents. However, a child may develop Fabry disease without the parents’ knowledge.
If both parents are carriers of the GLA gene, the daughter will have a 50 percent chance of developing Fabry disease. If a child has two X chromosomes, she may have less severe symptoms or not develop Fabry disease at all. In this case, the healthy X chromosome will compensate for the defective X chromosome.
Fabry disease cause by an alteration in the GLA gene, which provides instructions for making the enzyme alpha-GAL. Normally, males have one copy of the GLA gene and females have two copies. Females with Fabry disease usually have two copies of the GLA gene, and males can have one or both nonfunctioning genes. The changes in the GLA gene prevent the alpha-GAL enzyme from functioning properly.
Early symptoms of Fabry disease include a reddish to dark blue rash and skin lesions. These lesions can be flat or raised. Most commonly, males with type 1 Fabry disease have these lesions in the umbilical region. The disease also affects the heart.
Diagnosing Fabry disease in a family member can be easy and fast. Genetic testing and counselling are available to confirm or refute the diagnosis. The condition affects multiple members of a family, so genetic testing is essential for determining the exact cause of the disease. It is important to note, however, that a positive result in a newborn screening test is not conclusive.
The disease usually manifests in childhood or adolescence. Signs of the disease include pain in the extremities, dark red spots on the skin called angiokeratomas, reduced sweat function, and an opaque cornea. Patients also may experience gastrointestinal problems, fatigue, and even wheezing.
Treatment
A doctor can prescribe a variety of treatments to treat Fabry disease. The most common one is enzyme replacement therapy, which delivers enzymes to the body through an infusion. These treatments are usually given every few weeks. Another drug is called migalastat, which stabilizes enzymes that are not functioning properly. Both of these treatments have shown to improve symptoms.
The cause of Fabry disease is unknown, but it runs in families. It is an inherited disorder that results in the reduced activity of an enzyme called alpha-galactosidase A (a-Gal A). When a-Gal A is not functional, the enzyme’s substrate, GL-3, builds up in the body. This buildup causes symptoms and can result in organ damage.
Genetic testing is one method of diagnosing Fabry disease. It can determine whether or not a particular gene in a patient causes the condition. Other methods of diagnosing the disease involve enzyme activity tests and imaging tests. MRIs and computed tomography scans can help doctors understand the patient’s body better. Another test called an angiography, helps doctors look at the affected blood vessels.
Some patients may benefit from enzyme replacement therapy, which helps alleviate symptoms. Other treatments may include H2 blockers, which can ease symptoms in the gastrointestinal tract. Patients with abdominal symptoms may also benefit from eating small meals frequently. Laser treatments are not very promising without enzyme replacement therapy. However, liquid nitrogen treatments are used for Pedunculated lesions.
A multidisciplinary approach to Fabry disease treatment is necessary to ensure the patient’s quality of life. Treatment includes intravenously administered enzyme replacement therapy (ERT), conventional medical treatments, and adjunct therapies. There are currently three FDA-approved Fabry disease treatments: agalsidase beta, agalsidase alfa, and agalsidase alfa.
Cardiovascular treatment is another way to improve the outcome for patients with Fabry disease. Many patients develop cardiac complications in the course of their disease. If these complications are treated early, enzyme replacement therapy can help prevent or slow the progression of heart failure. However, this approach limit to the early stage of the disease.
Complications
If you suspect that you may have Fabry disease, you should consult with a genetic/metabolic specialist. They can help you better understand the condition and offer support and education. In some cases, referral to a GI specialist may help you manage chronic gastrointestinal disturbances caused by Fabry disease.
In addition to heart problems, Fabry disease may cause a number of other symptoms. Some people experience chronic fatigue, dizziness, headache, and general weakness. Other symptoms may include delayed puberty, hair loss, and malformations of the fingers and toes. The disease can also cause abnormal accumulations of lymph and lymphatic fluid in the body. These fluids can disrupt the normal drainage of lymph.
Fabry disease cause by a mutation in the gene GLA, located on the X chromosome. This gene produces alpha-galactosidase A, an enzyme that breaks down globotriaosylceramide. As a result, patients with Fabry disease have a lower level of this enzyme in their blood. This can lead to serious health problems and even death.
Some people with Fabry disease may develop angiokeratomas. These lesions can affect the arteries and the brain. The condition also causes ventricular hypertrophy, which mimics hypertrophic cardiomyopathy. This causes a reduced end-diastolic volume, impaired diastolic filling, and decreased cardiac output.
Early detection of kidney lesions is key in early stages. Regular assessments of protein and microalbuminuria are also helpful. Renal biopsy is a valuable diagnostic tool. Renal biopsy results provide histological information about kidney function and prognosis and can help guide treatment decisions in patients with early Fabry disease.
Although Fabry disease is a chronic disease, life expectancy is shortened. The prognosis is not uniform among patients, but patients with severe forms of Fabry disease often have a lower life span than patients with less severe forms. For these patients, the average lifespan is below 60 years. Most deaths from Fabry disease are due to cardiac failure or other cardiovascular complications.
Males with 1% activity of a-galactosidase A enzyme have a broader spectrum of symptoms. Males who have higher levels than these typically exhibit organ-specific symptoms. The symptoms in females are much less severe than in males, but the disease is not inherited from the father. However, a family history can help determine if you have the disorder.
