Fabry disease is caused by a mutation in the alpha-galactosidase-A gene (GLA). This gene codes for an enzyme active in lysosomes, the recycling centres within cells. Lysosomes contain more than 50 different enzymes that digest unwanted materials in cytoplasm. They are popularly referred to as "suicide bags" and are responsible for cellular homeostasis due their involvements in secretion, plasma membrane repair, cell signalling and energy metabolism. Mutations in genes for lysosomal enzymes are responsible for more than 30 different genetic diseases collectively known as lysosomal storage diseases.
With Fabry disease, as the gene for alpha-galactosidase-A is located on the X chromosome males are 2-3 times more likely to suffer from this condition than females. (Approximately 1 in 40,000 to 60,000 males have the disease compared to 1 in 117,000 females). Mutations of the GLA gene alter the enzymes translated structure preventing lysosomes from breaking down a fatty substance known as globotriaosylceramide. Subsequently fatty deposits accumulate in mainly the blood and blood vessel walls.
Symptoms are first experienced in early childhood and typically include episodes of pain, clusters of small, dark red spots on the skin (angiokeratomas), a decreased ability to sweat, and cloudiness of the front part of the eye. Due to the rarity of the disease, however misdiagnosis is common, particularly in early stages. Levels of the fatty substance increase over time, the blood vessels narrow decreasing both blood flow and reducing nourishment of tissues. This can lead to many life-threatening complications including kidney damage, heart attack and stroke.
Patients with Fabry disease have a reduced life expectancy, around 17 years shorter as compared to the general population. There is currently no cure for Fabry disease however patients are often successfully treated by enzyme replacement therapy (ERT). Research is currently being carried out into substrate synthesis inhibition and gene therapy.
Fabry disease can be diagnosed in males by enzyme assay to measure the amount of alpha-GAL enzyme activity in the blood. However due to the random nature of X-inactivation of one of the two copies of the X chromosomes in females, molecular genetic analysis of the GLA gene itself is required, particularly if the mutations have already been identified in male family members.
Black Swan’s proprietary Epiomic™ database can provide you with precise information regarding each of the individual symptoms and their frequency within sufferers of Fabry disease. This is critical for a disease with wide ranging clinical signs and symptoms that are commonly misdiagnosed.