Genetics of Fabry Disease

Like all genetic diseases, Fabry disease often poses a major concern for parents and caregivers of an affected child. Understanding the genetics of the disease can help in further family planning and in devising new therapies.

What causes Fabry disease?

Fabry disease is caused by mutations in the GLA gene, which encodes for an enzyme called alpha-galactosidase A (alpha-GAL). Alpha-GAL is responsible for breaking down a type of fat called globotriaosylceramide (Gb3 or GL-3). The mutations result in the alpha-GAL enzyme not functioning properly or not being made at all. As a result, Gb3 accumulates inside cells, leading to a range of problems including stroke, kidney disease, and heart attack.

How is Fabry disease inherited?

Fabry disease is an X-linked disease, i.e. the gene that is mutated is situated on the X chromosome. Chromosomes are structures within the cell that store genetic information. Humans have 22 pairs of autosomes (non-sex chromosomes) and one pair of sex chromosomes. Males have only one copy of the X chromosome while females have two.

I’m a female carrier of Fabry disease. What are the chances of my children being affected by the disease?

In female carriers of Fabry disease, one of the X chromosomes still contains the normal copy of the GLA gene, which somewhat compensates for the functions of the mutated copy.

If you are a female career of Fabry disease, these probabilities can be expected for each pregnancy:

• A 50% chance that a male child will be affected.
• A 50% chance that a female child will also be a carrier.

I’m a male diagnosed with Fabry disease. What are the chances of my children being affected by the disease?

Males have one X and one Y chromosome. Therefore, a mutation in the GLA gene on the single X-chromosome is enough to cause Fabry disease symptoms in males.

If you are a male diagnosed with Fabry disease, these probabilities can be expected for each childbirth:

• None of the male children is affected.
• All female children become carriers and may show mild symptoms.

Last updated: Sept. 3, 2019

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Fabry Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.