What is Fabry Disease


Fabry Disease:

Fabry disease results from abnormal deposits of a particular fatty substance (called globotriaosylcera-mide) in blood vessel walls throughout the body. The primary defect which allows this to occur is the inherited deficiency of the enzyme, alpha galactosidase A, which is normally responsible for the breakdown of globotriaosylceramide.

Metabolic Defect
The body continuously performs metabolic processes which produce, recycle and remove vital compounds. In patients with Fabry disease one such common compound formed of three sugars and a fatty substance (globotriaosylceramide) does not get broken down due to the missing or non-functioning enzyme alpha galactosidase A. Since this fatty compound (lipid) is not being broken down and removed, it begins to accumulate. Thus, Fabry disease is often referred to as a "storage disorder" due to this abnormal accumulation. In patients with Fabry disease, this accumulation occurs primarily in the blood and in the walls of blood vessels. As the abnormal storage of this fatty compound increases with time, the channels of these vessels become narrowed, leading to decreased blood flow and decreased nourishment of the tissues normally supplied by these vessels. This abnormal process occurs in blood vessels throughout the body, particularly affecting vessels in the skin, kidneys, heart, brain and nervous system.

Disease Inheritance
Fabry disease is an inherited disorder. The defective gene is on the X-chromosome, which is one of the two chromosomes that determine an individual’s sex. Females have two X chromosomes, one inherited from each of their parents. Males have one X chromosome inherited from their mother and one Y chromosome inherited from their father. A female with Fabry receive one X chromosome with a defective gene and one X chromosome with the normal gene, and thus often has some protection from the major manifestations of the disease. This is not always the case though as there is a high degree of variability in females. Males with Fabry disease receive only one abnormal X chromosome that contains the abnormal gene and thus express the disease.

All male and female children of an affected female have a 50% chance of inheriting the defective gene from their mother. If the father is the one carrying the Fabry gene all female children will inherit the defective gene and all male children will not. The inheritance pattern of Fabry disease is called X-linked inheritance. Fabry disease occurs in all ethnic groups. It is estimated that one person in 40,000 has Fabry disease.

Clinical Symptoms

Treatment
Pain associated with Fabry disease can be difficult to treat but usually responds to medications such as Tegretol (carbamazepine), Dilantin or Neurotin. Metoclopramide, Lipisorb (a nutritional supplement), Pancrelipase may be beneficial in treating Gastrointestinal hyperactivity. Food and Drug Administration (FDA) approved treatment for Fabry has demonstrated positive results. Enzyme Replacement Therapy (ERT) was approved in 2003.