Fabry Disease, also referred to as Anderson-Fabry Disease, is a rare genetic disorder that belongs to a group of disorders known as lysosomal storage disorders. It is caused by a mutation in the GLA gene that leads to a deficiency or malfunction of an enzyme called alpha-galactosidase A (α-GAL A). This enzyme is responsible for breaking down a particular type of fat called globotriaosylceramide (Gb3) or ceramide trihexoside.
As a result of the enzyme deficiency, Gb3 accumulates throughout the body, predominantly in small blood vessels and various organs such as the kidneys, heart, skin, and nervous system. This accumulation can lead to serious cellular dysfunction, inflammation, and tissue damage, giving rise to a multitude of symptoms.
Clinical manifestations of Fabry Disease typically begin in childhood or adolescence and vary widely in severity. Some common symptoms include episodes of severe pain or burning sensations in the hands and feet (acroparesthesias), skin rash (angiokeratoma), gastrointestinal disturbances, hearing loss, sweating abnormalities, kidney dysfunction, and cardiovascular complications, such as arrhythmias and heart attacks.
Fabry Disease is inherited in an X-linked manner, meaning the defective gene is located on the X chromosome. Consequently, it primarily affects males, while females carrying a single mutated X chromosome usually experience milder symptoms or may even be asymptomatic.
Currently, there is no cure for Fabry Disease. However, treatments aim to alleviate symptoms and slow down disease progression. Enzyme replacement therapy (ERT) is commonly used to supplement the deficient α-GAL A enzyme, reducing Gb3 buildup and improving clinical outcomes. Gene therapy and other experimental approaches are also being investigated for potential future treatment options.
