Fabry disease is a rare inherited genetic disorder in which patients have a deficiency or dysfunction of an enzyme called α-galactosidase A (α-GalA). This enzyme is essential for breaking down a fatty waste product called globotriaosylceramide (Gb3) in the cells of the body.
The genetic defect, which is on the X-chromosome, leads to accumulation of Gb3 within the cells of the body. This build-up results in a cytotoxic reaction causing malfunction of many cell types and organs, including blood vessels, skin, eyes, gastrointestinal system, kidney, heart, and the central nervous system. Fabry disease is also referred to as a lysosomal storage disorder, because the accumulation of Gb3 happens in a part of the cell called the lysosome.
Fabry disease can cause a wide range of symptoms affecting many parts of the body, including neuropathic pain, gastrointestinal problems, skin rash, tinnitus and more severe conditions such as heart disease and stroke. The disease typically begins in childhood and is slowly progressive, with burning sensations and pain in the hands and feet. In the absence of a family history of Fabry disease, the diagnosis of is often delayed due to the rarity of the disease and the non-specific nature of the symptoms.
The median prevalence of diagnosed Fabry disease is 1.0 per 100,000 in males and 1.9 per 100,000 in females. As the gene responsible for Fabry is found on the X chromosome (of which males have one, and females two), males with deleterious mutations have little or no residual α-GalA activity. Therefore, these male Fabry patients experience the full spectrum of disease symptoms. It is now widely accepted that women with Fabry disease are heterogeneous with respect to disease severity and may sometimes also develop life threatening complications of the disorder. Up to 70% of female carriers develop Fabry related symptoms at some points in their life.
The current treatment approach for Fabry disease is Enzyme Replacement Therapy (ERT). ERT supplies recombinant α GalA to the cells, which helps to improve or prevent deterioration of kidney function, heart function, and blood supply to the brain. ERT is only partly effective in Fabry disease, and requires intravenous treatment administration. Only one other therapy has been granted marketing authorization in the EU as an oral monotherapy for the long-term treatment of patients 16 years and older with a confirmed diagnosis of Fabry disease. Other treatments are aimed at relieving individual symptoms, such as opioids for severe pain. In advanced Fabry disease, hemodialysis and kidney transplantation may be necessary.