Background
The signs of Fabry disease were first identified in 1898 by two dermatologists working independently, Dr William Anderson in England and Dr Johannes Fabry in Germany.
They separately published papers in which they described patients with skin lesions, known as angiokeratomas, which are now recognized as a common sign of Fabry disease. The disease has a number of names, including angiokeratoma corporis diffusum, alpha-galactosidase A deficiency, and was for many years known as Anderson-Fabry disease, but is now usually referred to simply as Fabry disease.
Dr Johannes Fabry (left), and Dr William Anderson (right).
Further research established that Fabry disease results from abnormal deposits of a fatty substance, known as globotriaosylceramide (Gb3, sometimes abbreviated as GL-3, and also known as ceramide trihexoside [CTH]). Normally, Gb3 is metabolized (broken down) by an enzyme called alpha-galactosidase A (a-Gal A). In people with Fabry disease, the gene that would normally tell the body to produce this enzyme is altered (often called a gene mutation). This alteration means that the enzyme does not work properly or is completely absent. This in turn leads to a build-up of Gb3 in cells of blood vessels, kidneys, brain, eyes and other organs. It is because of this build-up that Fabry disease is referred to as a storage disorder, and because the build-up happens in a part of the cell called the lysosome it is called a lysosomal storage disorder (also known as lysosomal storage disease).
In normal cell function Gb3 is broken down and removed from the cells or recycled. However, without the enzyme, Gb3 gradually builds up in the cells and affects their normal function. It's a bit like in a household when the trash bags containing the trash produced by the family are filled up and taken outside to the bin. If the bin is not put out for collection the trash will gradually build-up over time. Eventually they will take up all the space, leaving no room to do anything and causing lots of problems.
Although there is no cure for Fabry disease, we now know much more about symptoms and how to manage them. Also, research and development continues into therapies that can have a beneficial effect for people with Fabry disease.
Incidence
Fabry disease is rare but equally affects all ethnic groups with an estimated incidence of approximately one in 117,000 in the general population. Males with Fabry disease will almost always display the characteristic signs and symptoms of the condition. Females however, have a much more variable presentation, where some develop symptoms similar in severity to affected males, others have a milder course often with a later age of onset, and still others never develop symptoms at all.
Fabry disease is the second most common lysosomal storage disorder after Gaucher disease. Because the signs and symptoms of Fabry disease are so varied, a definitive diagnosis often takes several years. Therefore individuals with Fabry disease are often misdiagnosed or may be completely undetected.
Lysosomal Storage Disorders
Fabry disease belongs to a group of disorders known as lysosomal storage disorders (LSDs). Like Fabry disease, many LSDs are named after the people who discovered them, such as Gaucher disease, Hunter syndrome and Hurler disease.
LSDs are a group of over 45 related conditions characterized by defects in lysosomal function due to the inheritance of altered genes.
A lysosome is part of the structure of a cell and is responsible for breaking down certain types of substances so that they can be discarded or reused by the body. These substances are broken down by enzymes in the lysosomes. The altered genes associated with LSDs result in a specific defect in enzyme activity, leading to a build-up of waste substances in body tissue. Many LSDs are similar in character and are usually classified by the type of substance that builds up as a result of the malfunction.
As the substances build up over time, the symptoms and progression of the disease often become worse. The exact progression of symptoms depends on the specific disease, its severity and the individual involved. It is also possible for affected members from the same family to show very different symptoms and at different times.
Currently, the treatment of LSDs tends to be based on the management of symptoms as well as preventing or reversing the decline in organ function.
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