Differences in Males and females

Because of the way it is inherited, Fabry disease can affect males and females differently.

The gene that causes Fabry disease is located on the X chromosome. Males inherit an X chromosome from their mothers and a Y chromosome from their fathers. Females inherit an X chromosome from each parent.

A male has one X chromosome and one Y chromosome. Therefore, when a male inherits an X chromosome with the defective gene, he produces little or no alpha-GAL enzyme, and he develops the symptoms of Fabry disease. A female has two X chromosomes, so even if she inherits the Fabry gene, she has a second gene that could produce alpha-GAL.

However, females may still experience symptoms because of a process called X-inactivation. While each cell in a female’s body contains two X chromosomes, one is turned off, or inactivated, while she is developing in her mother’s womb. Statistically, half her cells should have one X chromosome working, and half should have the other working. But, like flipping a coin, 50-50 odds do not always result in a perfect 50-50 split.

Each organ in a female’s body has its own X-inactivation pattern. For example, in a female who has Fabry disease, one organ may have 60% of her healthy X chromosome working, while another organ may have only 30% working. A female’s specific X-inactivation pattern can cause her to have some Fabry symptoms, but not others. It can also determine how severe those symptoms will be.

It is important to understand that some women can be at risk for developing life-threatening complications, even if they do not experience typical early symptoms such as pain.

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