What is Fabry Disease?
Fabry Disease is a rare lysosomal storage disorder. It is a genetic condition that occurs because there is a mutation in the DNA – in this case a mutation on an X-chromosome. It can be inherited, or, like me, you may be the first in your family to be born with it.
Fabry Disease is also known as Anderson-Fabry Disease. It was first discovered in 1898 by two scientists who were working independently. William Anderson, UK identified a systemic disorder in a 39 year old man and Johannes Fabry, Germany identified a similar condition in a 13 year old boy. It wasn't until the 1960's and 70's though that the accumulation of Gb3 and the deficient enzyme α-Gal A were identified as the causal factors of this condition.
So why does Fabry cause problems? I’ve broken this down into bite-size steps as this is how I came to understand it:
The mutation that causes Fabry is in the GLA gene.
The GLA gene normally produces an enzyme known as alpha-galactosidase (α-Gal A).
The mutation causes a reduction in the production of, or a total absence of, the α-Gal A enzyme.
α-Gal A is needed to breakdown a glycolipid (a type of fat) known as globotriaosylceramide (Gb3 or GL-3).
Because there is little or no α-Gal A, there isn't anything to break down the Gb3 fat.
Because it isn’t broken down the Gb3 builds up incertain cells inside our bodies, in for example our heart, kidneys, brain, skin, eyes, digestive system or nervous system and causes problems.
Where we are affected will depend which of our cells have the mutated gene. This is where the genetics become important.
Fabry is generally divided into two forms – classical and non-classical:
This form of Fabry Disease usually becomes apparent during childhood, with severe pains in the hands and feet, issues with the digestive system, frequent illnesses and/or skin issues. Without treatment it can progress to issues with major organs including the heart, kidney and brain. It was once thought that only men would have the classical form of Fabry Disease as they have little or no α-Gal A enzyme activity. However, it is now known that females can have this more severe form of Fabry, and it should be treated accordingly.
The non-classical form of Fabry is also called late-onset. This is because symptoms occur when a person is older, without any of the typical childhood symptoms. This form of the illness occurs when a person has enough enzyme activity to produce a slower progression of the disease.