Fabry disease in women: genetics and disease progression
Did you know that women with Fabry, on average, get diagnosed with Fabry 10 years after first experiencing symptoms? It was once believed that women with Fabry were only carriers of the disease, passing the disease on to their male children but not experiencing the effects of the disease themselves. That myth has been disproven. In the last few decades, research on Fabry disease has shown that the majority of females with Fabry experience symptoms and effects. Women are not just carriers of Fabry disease, but are living with the effects of Fabry themselves.
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Because it was incorrectly thought that women were only carriers of Fabry disease, it may not be common knowledge that this rare disease can affect women. If you are a woman with Fabry disease and experience its effects, you are part of the 70% that do, making you among the majority of women with Fabry.
Science of Fabry
In people with Fabry disease, a genetic variation in the GLA gene affects alpha galactosidase, or alpha-Gal A, enzyme activity. Alpha-Gal A usually travels to the lysosome, a recycling center in the cells, to break down fatty substances, or substrates. But in Fabry, GLA gene variants result in an absent or deficient alpha-Gal A enzyme. Because the enzyme is not in the lysosome breaking down fatty substances, or substrates, they build up instead. The buildup affects all types of cells, causing damage that leads to the signs and symptoms of Fabry disease.
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Diagnosis for women
For women, enzyme activity doesn’t tell the whole story. Symptoms can still develop, and Fabry can still be severe and progressive, in women with normal to detectable levels of alpha-Gal A enzyme activity. So while an enzyme blood test may show that you have alpha-Gal A enzyme activity, that doesn’t mean that you don’t have Fabry. And it doesn’t mean that your body is working the way that it should. A genetic test, on the other hand, can determine whether women have Fabry disease—in fact, this test is required to diagnose Fabry in women.
Genetics of Fabry
Understanding the difference between males and females with Fabry disease starts with DNA. Genes get passed down from parents to their children, and so can Fabry, a genetic disease. Genetic variants that can cause Fabry disease are located on the X chromosome. Fabry disease is an X-linked genetic disorder passed down through the X chromosome. Women have two X chromosomes, while men have one X and one Y chromosome.
An affected male passes his GLA gene variant down to all of his daughters, because females always inherit X chromosomes from their fathers. Women with Fabry disease pass GLA gene variants down to their children, who all have a 50/50 chance of inheriting the disease whether they are male or female.
In other words, if you are a daughter of a father with Fabry disease, then you have a 100% chance of inheriting the disease from him. If you are a daughter of a mother with Fabry disease, you have a 50% chance of inheriting the disease.
The genetics of Fabry disease mean that men and women with Fabry inherit the disease differently. Men have one X chromosome, so if that X chromosome has one of the gene variants that cause Fabry, it affects all of their cells. On the other hand, women have two X chromosomes, so in every cell, only one of the two X chromosomes may become activated. Cells with an activated X chromosome are affected by Fabry disease.
Whether a woman inherits Fabry disease from her mother or her father does not change how much, or to what severity, she experiences the disease.
Symptoms of Fabry disease in women
Women with Fabry can experience a variety of symptoms, just as men can. There is a wide range of symptoms, and they can range in severity from mild to severe. Because manifestations of Fabry disease can affect many parts of the body, it is considered a whole-body disease. One survey looking at pain intensity, duration, and frequency as a result of Fabry disease in both genders showed that pain ratings from women were virtually indistinguishable from those of men. There are many ways that Fabry can affect the body, including:
- Protein in the urine
- Decreased kidney function
- Kidney failure
- Irregular heartbeat (fast or slow)
- Heart attack or heart failure
- Enlarged heart
- Transient ischemic attack (TIA)
- Nerve pain
- Intolerance to heat, cold, or exercise
- Pain or burning in the hands and feet
- Vertigo/feeling dizzy
- Difficulty breathing, shortness of breath
- Chronic cough
- Feelings of guilt, worry, depression, isolation, and/or fear
- Nausea, vomiting, cramping, and diarrhea
- Pain/bloating after eating, feeling full after a small amount of food
- Hearing loss, ringing in the ears (tinnitus)
- A whorled pattern in the cornea
- Fabry cataracts
- Sweating less than normal or not at all
- Small, dark, red spots, mostly appearing between the belly button and upper thighs
- Fatigue—a deep feeling of tiredness
Fabry disease requires consistent monitoring
Changes happening in your body may not be obvious. And Fabry disease is progressive, so symptoms tend to change over time. Work with your healthcare provider to manage your symptoms that are, or could be, affecting your quality of life.
While there is no known cure for Fabry disease, there are disease management options to talk to your doctor and healthcare team about.
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