Fabry disease is a rare genetic disorder involving a deficiency or dysfunction of α-galactosidase A (α-GalA) an enzyme that normally breaks down a fatty waste product known as Gb3 in the cells of the body.
Over time, this may result in a build-up of Gb3 deposits throughout the body, particularly in the kidneys, heart and nervous system.
The symptoms range from pain in the hands and feet, eye and stomach problems, to stroke and kidney failure, depending on which organs are affected. Because the symptoms are non specific, Fabry disease is often undetected or misdiagnosed. As the disease is progressive, early diagnosis is essential to manage the symptoms as soon as possible and reduce the risk of developing serious complications.
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.
Current treatment approaches for Fabry disease include Enzyme Replacement Therapy (ERT). ERT requires intravenous infusions to replace the deficient enzyme in the cells with a genetically engineered form. 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.