How Is Fabry Disease Inherited From a Mother?

If you are a woman with Fabry disease, there is a 50% chance with each pregnancy that you will pass the condition to your child. This 50% chance is the same whether you have a boy or a girl ^[1][2]. (Note: Inheritance from a father with Fabry disease works completely differently—fathers pass the gene to 100% of their daughters and 0% of their sons.)

To understand why this happens, it helps to look at how our chromosomes work.

The X Chromosome Connection

Fabry disease is caused by a genetic change (mutation) in the GLA gene, which is located on the X chromosome ^[1].

Biological females typically have two X chromosomes (XX). If you have Fabry disease, one of your X chromosomes has the genetic change, and the other X chromosome usually does not ^[2].

Biological males typically have one X and one Y chromosome (XY).

When you have a child, you randomly pass on one of your two X chromosomes.

• If you pass on the X chromosome without the mutation, your child will not inherit the Fabry mutation.
• If you pass on the X chromosome with the mutation, your child will inherit the genetic mutation that causes Fabry disease ^[1].

Because it is a random flip of a coin every time, the chance is exactly 50% for each and every pregnancy.

How It Affects Sons vs. Daughters

While the chance of inheriting the gene is the same (50%) for boys and girls, the way the disease might affect them can be different.

If a Son Inherits the Gene

If you have a son and he inherits the mutated X chromosome from you, he will have Fabry disease ^[2]. Because males only have one X chromosome, they do not have a second “backup” X chromosome to compensate. Because of this, males with the gene typically experience more classic, predictable symptoms of the condition ^[2]. These symptoms often start in childhood or adolescence and can include burning pain in the hands and feet, decreased sweating, skin rashes, and eventual heart or kidney issues.

If a Daughter Inherits the Gene

If you have a daughter and she inherits the mutated X chromosome, she will also have Fabry disease. In the past, women were often called “carriers” and thought to be symptom-free. We now know this is incorrect. Women with the Fabry gene can experience a wide range of symptoms—from very mild to severe organ involvement (including the heart and kidneys) ^[3][4].

This wide range happens because of a process called X-chromosome inactivation ^[3]. Since females have two X chromosomes, the body randomly “turns off” one X chromosome in every cell. If a daughter’s body happens to turn off the healthy X chromosome in most of her cells, she may develop more severe symptoms. If the mutated X chromosome is turned off in most cells, her symptoms may be milder ^[3]. Importantly, this process happens differently in different parts of the body. For example, the healthy chromosome might be turned off in the heart but not the kidneys, which explains why symptoms in women can be so specific to certain organs.

If You Already Have Children

If you have just been diagnosed and already have children, it is natural to feel anxious about their health. The first step is to discuss your diagnosis with their pediatrician and a genetic counselor.

• Testing: Your children can be tested to see if they inherited the gene. A genetic counselor can help you decide the best age to test them. For boys, testing might be considered earlier in childhood since symptoms often begin sooner. For girls, the timing of testing might depend on whether they are showing symptoms.
• Treatments are available: If your child does test positive, it is important to know that Fabry disease is manageable. There are specific treatments available, such as enzyme replacement therapy (ERT) and chaperone therapy, which can help prevent or delay organ damage and manage symptoms.

Planning for Future Pregnancies

If you are planning to have children, it is highly recommended to speak with a genetic counselor ^[5]. A genetic counselor is a specialized healthcare provider who can:

• Explain your specific genetic test results.
• Discuss your personal risks for future pregnancies.
• Walk you through family planning options, including advanced reproductive technologies like preimplantation genetic testing (PGT), which can screen embryos for the Fabry gene before pregnancy.