Genetics and Fabry Disease

Fabry disease is a genetic disease passed down from parents to children. To better understand how Fabry disease is inherited, and who may be affected in the family, a basic understanding of genetics and inheritance is helpful.

^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.

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.

^Inheritance

The Fabry gene is passed on in one of two ways:

1) A father with Fabry disease (Affected Father) will pass the gene onto all of his daughters and none of his sons (see the figure below). As discussed above, the Fabry gene is located on the X chromosome and a man will only pass his X chromosome (which carries the Fabry gene) on to his daughters. His daughters will likely not have Fabry disease but will be Fabry carriers. This is because the daughters' other X chromosome will likely carry a healthy gene that is capable of making alpha-GAL. However, some female Fabry carriers experience symptoms of Fabry disease. For more information about affected female carriers, read Fabry disease in men and women.

X^r= chromosome w/ Fabry gene

2) If a mother carries the Fabry gene (Carrier Mother), there is a 50% chance that she will pass the gene onto her sons or daughters (see the figure below). Her sons who inherit the gene will have Fabry disease. Her daughters who inherit the gene will be carriers.

X^r= chromosome w/ Fabry gene

^{Fabry Disease in Men and Women}

Fabry disease can affect anyone who inherits the faulty gene - both males and females. Virtually all males with the Fabry gene develop the disease and are likely to express some or many of the classic Fabry symptoms. In women with the Fabry gene, however, symptoms can range from none (in asymptomatic carriers) to very serious manifestations similar to those seen in males. That's because the level of symptom severity often depends on the amount of alpha-GAL enzyme produced in the body. Females with the faulty gene can have anywhere from near-normal levels of alpha-GAL to no active enzyme. Males, on the other hand, usually have little or no active alpha-GAL and are more likely to experience more severe symptoms than females.

^{Tracing Fabry Disease in Your Family}

Fabry disease is inherited, so if one person in a family has the disease, others may have the disease as well. The earlier Fabry disease is diagnosed, the sooner doctors can begin monitoring and treating the associated symptoms.

A medical family tree can help you understand how Fabry disease has affected relatives, both living and deceased, as well as how the gene may affect generations to come. The link below provides an example of a medical tree that you can download to your computer. In this family tree, you can fill out health information about yourself, your immediate and extended family, and family members from past generations. It is recommended that you seek the assistance of a health care provider or a medical genetic counselor to complete this historical account.

Click here to download a medical Family Tree Chart (PDF)

For more information on how Fabry Disease is inherited, visit Genzyme’s Fabry Community website.