Fabry disease (Fabry syndrome, Fabry disease or Fabry Anderson disease) is a rare metabolic disease in which a gene mutation causes an enzyme defect. The result is a reduced degradation of metabolites and their increased storage in the cell. As a result, the cell is damaged and dies. As a result, organs are damaged and depending on organ damage, a variety of symptoms can occur.
The cause of Fabry disease is a missing enzyme, α-galactosidase A. This enzyme occurs within the cells in certain compartments, the lysosomes, where it is needed for the cleavage of glycosphingolipids. Glycosphingolipids are a group of sugary fats needed to build the cell. This enzyme is missing due to a genetic defect, as a result of which various metabolites (especially globotraosylceramide) accumulate within the cells and damage them. As a result, the cell dies and it comes to organ damage, and dysfunction. This type of disease is referred to as lysosomal storage disease because the metabolic products in the cell accumulate within the lysosomes.
Fabry disease is inherited as an X-linked disease. Sons of sick fathers are healthy because they only get the Y chromosome from their father, whereas the daughters always get sick because they inherit the X chromosome. The fact that sick men have only one X chromosome with the defective gene, the disease is much more severe in them than in women. Women still have a second X chromosome that can partially compensate for the defect
An early diagnosis is very important for the treatment of Fabry disease, because the earlier the symptoms are treated, the slower the disease progresses. There are certain centers that specialize in the treatment of the symptoms of Fabry disease and to whom they should definitely turn. Because Fabry disease is a multi-organ disease, treatment is provided by a team of cardiologists, kidney specialists, kidney specialists and other specialists.
In addition to relieving the symptoms, the therapeutic approach has for some years mainly focused on replacing the missing enzyme with an artificially produced α-galactosidase. This enzyme replacement therapy causes the metabolites to degrade and not deposit in the organs, thereby improving the patients' symptoms. Early treatment can prevent damage to the organ systems and patients can lead an almost normal life.
Fabry disease is a disease that affects several organ systems simultaneously, referred to as a so-called multi-organ disease. Accordingly, the accompanying symptoms are different. The most common ones include:
Pain in the hands and feet
burning pain in the body tips (acres): nose, chin, ears
Changes in the skin
Discomfort of the digestive tract
Many patients with Fabry disease are affected by symptoms in the eyes. Characteristically, clouding of the cornea occurs through fine deposits, which, however, do not significantly affect vision. The deposits are cream-colored and distribute themselves vortex-shaped over the cornea. This disease is called Cornea verticillata. Also, the lens of the eye can be affected by the turbidity, one then speaks of so-called Fabry cataracts. The ophthalmologist diagnoses the changes in the eyes by examining them with a slit lamp, which allows the cornea and the lens to be magnified.
Changes in the skin are typical symptoms of Fabry disease. Often dark red to dark purple dots appear, which spread like small wart-like elevations over the skin. These are angiokeratoms, a benign skin tumor. The points can grow up to several millimeters and occur anywhere on the body.
Fabry disease often causes discomfort to the blood vessels, which can lead to circulatory disorders in the brain and in the worst case to a stroke. The risk for patients with Fabry disease to suffer a stroke before the age of 50 is significantly increased. As a result, a stroke, in addition to kidney failure, is one of the leading causes of death in Fabry syndrome.
Fabry disease is often accompanied by muscle pain. These mainly affect the hands, feet and face (nose, chin, ears). The burning pain can not be alleviated in many cases by conventional painkillers, in severe cases, therefore, the doctor prescribes opiates. In addition, it often comes to so-called paraesthesia, these are sensations such as numbness, tingling or running ants.
Fabry disease describes a serious condition that causes severe damage to the kidneys, heart and brain at an early age. Due to the reduced enzyme activity, fats are deposited in the vessels and organs, which causes more and more damage to the organs and finally completely loses their function. If the disease remains undetected or if no treatment is given, the patients in Fabry disease often die prematurely from heart disease, chronic kidney failure or stroke. Left untreated, sufferers have greatly reduced life expectancy, which is only around 40 to 50 years. If the disease is detected early and is immediately started on appropriate treatment in the form of enzyme replacement therapy, patients will have a near-normal life expectancy not far below the median age.
Diagnosing Fabry disease is not always easy, and patients often have a long ordeal until the symptoms can be attributed to the condition. It often takes several years for a doctor to make the correct diagnosis. If Fabry disease is suspected, the doctor will diagnose it by means of a series of laboratory tests for which a blood sample must be taken. After confirming the diagnosis, the doctor will usually refer the patients to certain clinics specializing in the treatment of lysosomal storage disorders.
There are a number of molecular genetic tests that can confirm the diagnosis of Fabry disease. First of all, a simple enzyme test can clarify whether a defect of α-galactosidase is present. In men, a positive test result (ie a reduced activity of α-galactosidase) is usually sufficient to determine the disease. Diseased women may nevertheless have a normal activity of the α-galactosidase enzyme in the blood, therefore, in such cases additionally carried out a gene analysis. Genetic analysis can be used to show if the woman has a disease-causing mutation in the α-galactosidase gene.