Fabry Disease : General Disease Information
|The enzyme involved in Fabry disease can be abbreviated in several different ways. You may see α-galactosidase A referred to as α-GAL, α-GAL A, or GLA. Likewise, the substrate that accumulates in Fabry disease, globotriaosylceramide, can be abbreviated as GL-3 or Gb3. This website will use α-GAL and GL-3 to refer to the enzyme and substrate, respectively, involved with Fabry disease.|
Fabry disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called α-galactosidase A (α-GAL). The role of α-GAL within the body is to break down a complex lipid called globotriaosylceramide (GL-3). Reduced or absent levels of α-GAL activity leads to the accumulation of GL-3 in the affected tissues, including the central nervous system, heart, kidneys, and skin. This accumulation of GL-3 is believed to cause the various symptoms of Fabry disease, including pain, kidney failure, and increased risk of heart attack and stroke.
It is currently estimated that Fabry disease affects approximately 5,000 to 10,000 people worldwide. However, several literature reports suggest that Fabry disease may be significantly under diagnosed, and the prevalence of the disease may be much higher.
| 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 and may be amenable to chaperone therapy.
Fabry disease is an X-linked recessive genetic disorder that affects both men and women. Most individuals with Fabry disease have missense mutations in the GLA gene. Missense mutations can alter the structure of α-GAL, which results in the accumulation of the enzyme in a part of the cell called the endoplasmic reticulum (ER). As a result of the accumulation of α-GAL in the ER, the enzyme is unable to reach the lysosome, the part of the cell where α-GAL does its work of breaking down substrate.