Fabry Disease : General Disease Information

	Pharmacological Chaperones To learn more about pharmacological chaperones for lysosomal storage disorders, click here (pdf - 3.4MB).

Fabry disease is an inherited genetic disease caused by diminished or absent levels of a key metabolic enzyme called α-galactosidase A (α-GAL). In most Fabry patients, missense mutations (genetic mutations that alter the structure of the protein that is produced) alter the structure of α-GAL, which results in the accumulation of the protein in the endoplasmic reticulum and premature degradation. As a result, α-GAL is unable to reach the lysosome – the area of the cell where the enzyme does its work. Reduced or absent levels of α-GAL activity leads to the accumulation of a complex lipid called globotriaosylceramide (GL-3) in the affected cells.

What’s Missing in Fabry disease? Historically, Fabry disease has been described as a disorder caused by a missing enzyme. While some individuals do not make any enzyme, many individuals with Fabry disease do make enzyme. For more information on “What’s Missing” click here (pdf - 6.5MB).

The accumulation of GL-3 leads to disease in the central nervous system, heart, kidneys, and skin. Patients with Fabry disease experience pain, clouded vision, and kidney failure, and also have an increased risk of heart attack and stroke. It is estimated that Fabry disease affects about 10,000 people worldwide, but these numbers do not account for the prevalence of later-onset Fabry disease, which is gaining in recognition.