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.1
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Dr Johannes Fabry (left), and Dr William Anderson (right).
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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 (disorder) 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.
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.2.3 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).
It’s a bit like in a household when the bin bags containing the rubbish produced by the family are filled up and taken outside to the bin. If the bin is not put out for collection the rubbish will gradually build up over time. Eventually the rubbish takes up all the space, leaving no room to do anything and causing lots of problems. It is the same principle in human cells - 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.
Studies then identified the alteration in the gene and this helped in the diagnosis of Fabry disease and paved the way for the development of enzyme replacement therapy.
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.