Medical Genetics and Genomics

Fabry Disease

Fabry disease is a genetic condition that results in reduced activity of an enzyme in the body called alpha-galactosidase A (alpha-Gal A). The purpose of alpha-Gal A is to break down a certain lipid, or fatty substance, called globotriaosylceramide (GL-3). When there is not enough a-Gal A, the GL-3 builds up in the body, especially in the vessels of the kidney, heart, nervous system, and skin; this build-up causes the symptoms of Fabry disease.

Classic Fabry disease usually begins in childhood or teenage years. These symptoms include episodes of severe burning pain in the hands and feet called acroparasthesias, small red raised spots on the skin called angiokeratoma, a characteristic change in the cornea of the eye that does not affect vision (corneal whorling), gastrointestinal symptoms (diarrhea, bloating, and pain), and decreased sweating. Adults with Fabry disease can develop heart disease, strokes, and kidney failure.

Late-Onset Fabry disease manifests in adulthood and usually lacks the classic symptoms such as acroparasthesias and angiokeratomas, and mainly affects the kidney and the heart. The symptoms in females with Classic and Late-Onset Fabry disease (also known as “heterozygotes”)vary. Females may have mild symptoms of the disease or the disease may present more severe as in males. There is no way to predict the clinical picture in a female.

Fabry disease affects males differently than it does females due to the way it is passed through families (the inheritance), which is called X-linked inheritance.

Fabry Disease Treatment

There is an FDA-approved treatment for Fabry disease, which replaces the missing alpha-Gal A enzyme. This treatment is called enzyme replacement therapy (ERT) and is given by intravenous (IV) infusion every two weeks for life. The goal of treatment is to slow disease progression and improve Fabry symptoms.