Genetics and Fabry Disease

Fabry disease runs in families

Fabry disease is an inherited disorder, which means it is passed down from a parent to his/her children, and multiple people can be affected in a family. Fabry disease is very much a family disease because not just immediate family members are affected, but extended family members can be affected as well.

To understand Fabry disease and how it affects your family, you should know a little about genetics and how genes work.

Defining genetics and genes

Genetics is the branch of biology that studies the passing on of traits and features from parents to children. These traits are called “genetic” because they’re determined by tiny structures within human cells called genes.

  • Genes carry the instructions for building all the cells of the body. They determine things like our physical characteristics (such as eye and hair color) and physical functions such as metabolic processes (for example, turning food into energy).
  • All the genes in the human body (there are 20,000 to 25,000!) are contained on structures known as chromosomes.
  • Human cells each contain 46 chromosomes—or 23 pairs; we inherit one chromosome in each pair from our mother, the other one from our father.
  • Two chromosomes (one pair) of those 23 pairs determine the individual’s sex. They are called the X and Y chromosomes (also called the sex chromosomes).
  • Women have two X chromosomes (XX) in each of their cells, and men have one X chromosome and one Y chromosome (XY).

Fabry disease and X & Y Chromosomes

The genes on the X and Y chromosomes serve many purposes. For example, the gene that allows us to see color is located on the X chromosome—as is the gene associated with Fabry disease. This makes Fabry disease an “X-linked” condition.  In people with Fabry disease, this gene on the X chromosome does not function properly, so the body does not make enough alpha galactosidase A (alpha-GAL)—an important enzyme. This deficiency of enzyme causes a substance called globotriaosylceramide (GL-3) to gradually build up in the cells, which may eventually result in serious complications in the heart, brain and kidneys.

Because the gene associated with Fabry disease is located on the X chromosome (sex chromosome), Fabry disease may present differently in men than in women:

  • Because men have only one X chromosome in each cell, they have only one copy of the gene associated with Fabry disease. If the gene is altered, they usually have little to no active alpha-GAL enzyme.
  • Because women have two X chromosomes in each cell, they can have one normal and one altered copy of the gene associated with Fabry disease. This can allow them to produce some of the alpha-GAL enzyme; therefore women can experience the same symptoms males do, but not always to the same extent.