Fabry Disease is an inherited disorder that was once thought to affect only males. Females were called 'carriers' because it was believed that they carried the gene for the disorder without developing symptoms.

In the past decade, research on Fabry disease has increased dramatically.

New research is demonstrating that most females with the Fabry gene do, in fact, have a wide range of symptoms. These symptoms vary from one female to another, more than they vary among males. They range from mild to severe, may start later in life, and may affect different organ systems in different people. The effects of the Fabry gene on an individual female depend on a number of factors.

What is X-inactivation?

Each cell in a female's body contains two X chromosomes, but one is 'inactive' or 'turned-off' through a normal process called X-inactivation.

Random X-inactivation means that each X-chromosome has a 50% chance of being the active chromosome or the inactive chromosome in that cell. The selection is completely random. Therefore, if one of the X chromosomes carries the Fabry mutation, there is a 50% chance the Fabry chromosome will be turned on in the cell and a 50% chance it will be turned off. Since ½ of the cells produce normal enzyme and the other ½ do not, this tissue will have 50% of the normal α-GAL level, and should not experience Fabry symptoms.

Each organ in a female's body has its own X-inactivation pattern. Sometimes, a woman's X-inactivation pattern is not random and the distribution of cells active vs. non-active is not evenly distributed throughout their body. For unknown reasons, there may be more cells with the 'Fabry X' turned on, and fewer cells with the healthy, or 'non-Fabry X' turned on. When this is the case, any tissues containing these cells will have an uneven distribution of enzyme. In other words, rather than 50/50, she may have 70% of her cells with no enzyme, and only 30% with enzyme. 

           Normal (left), Mosaic (right)

           (Reprinted with permission from NEFSG)