Genetics and Fabry Disease

Fabry disease runs in families

Fabry disease is an inherited disorder. The gene that causes Fabry is passed down from a parent to his or her children. If one person in a family has Fabry disease, other family members (including siblings, children, parents, aunts, uncles, and cousins) may also be at risk. This makes Fabry very much a family disease — not just immediate family, but extended family as well. Fabry disease is considered to be X-linked, which means that the defective gene is located on the X chromosome, and therefore is inherited through the mother. To understand this better, it is helpful to understand a little about genetics.

Genetics

All of our hereditary information is contained on genes. We have genes that determine our physical characteristics like our hair color, eye color, height, etc. We also have genes that are responsible for specific functions such as our metabolism and growth.

All of our thousands of genes are contained on chromosomes. Each human cell contains 46 chromosomes (23 pairs). We inherit 23 chromosomes from our mother and 23 from our father for a total of 46 chromosomes. Two of the 46 chromosomes (or one pair) are called the sex chromosomes and are referred to as either an X or a Y chromosome. Women have two X chromosomes (XX) and men have one X chromosome and one Y chromosome (XY). Since women only have X chromosomes (XX), they will always pass an X chromosome to their children. On the other hand, men can pass an X or a Y chromosome to their child. If a man passes the X chromosome to his child, the child will be female. If a Y chromosome is passed on, the child will be male. It is completely random whether a man will pass an X or Y chromosome to his child.

Fabry and the X chromosome

The X and Y chromosomes are called sex chromosomes because most of the genes located on them are involved with determining a person's sex and sexual function. What may be confusing is that, while some genes on the X chromosome are responsible for sexual function and fertility, there are also other genes located on this chromosome that have nothing to do with sex. For example, the gene that helps our blood to clot and the gene that allows us to see color are located on the X chromosome. Likewise, the gene that makes alpha-GAL is located on the X chromosome. In patients with Fabry disease, this gene does not function properly and the body does not make sufficient quantities of alpha-GAL.

What does it mean to be a “carrier”?

Having the Fabry gene on your X chromosome means you are a “carrier” of the Fabry gene. What impact this has on you and your children — and the chances that you or they will develop Fabry disease — depends to some extent on whether you are male or female.

  • Male carriers pass the Fabry gene on to all of their daughters, but none of their sons. They are very likely to develop Fabry symptoms.
  • Female carriers have a 50% chance of passing the Fabry gene on to daughters or sons. Their chances of developing Fabry symptoms are variable.

Inheriting Fabry disease

Fabry disease is caused by a mutated gene that does not produce sufficient quantities of the enzyme alpha-galactosidase A (pronounced al-fa-ga-lak-toe-si-daze A) or alpha-GAL. Fabry disease can affect anyone who inherits the defective gene: that means both males and females of any ethnic group. The degree to which a person experiences the symptoms of Fabry disease depends on the amount of alpha-GAL enzyme they have. Females with the defective gene can have anywhere from near normal levels of alpha-GAL to no active enzyme. Males, on the other hand, typically have little to no active alpha-GAL, and can experience more of the classical signs and symptoms of Fabry disease. Therefore, females sometimes experience the same symptoms males do, but not always to the same extent. Fabry disease is inherited, so if one person in a family has the disease, others likely will as well. That is why it is important to develop a medical family tree.