Fabry disease is a rare genetic disorder that is caused by mutations in the GLA gene. The body uses the instructions that this gene provides to make an enzyme (alpha-galactosidase A) that breaks down fatty substances called globotriaosylceramide (Gb3 or GL-3). Mutations in GLA mean that the enzyme cannot function properly. As a result, Gb3 builds up in cells and tissues, interfering with function, and causing the symptoms of Fabry disease.
Who develops Fabry disease?
The GLA gene is located on the X-chromosome. Women have two X-chromosomes (one that they inherit from each parent). Doctors thought for many years that women didn’t develop symptoms of Fabry disease unless they inherited two copies of a disease-causing mutation. This was because the healthy gene on the second X chromosome would compensate for the faulty one. Men have only one X-chromosome and a Y-chromosome. They develop the disease if they inherit a single copy of the disease-causing mutation from their mother.
It now is clear that women with a single copy of a disease-causing mutation also can develop the symptoms of Fabry disease. Female patients and their physicians need to be aware of this possibility. This happens because both X-chromosomes are not active in every cell. Through a process called X-inactivation, cells “turn off” or inactivate one of X-chromosomes in different cells of the body. If the X-chromosome that is silenced in most cells contains the disease-causing mutation, a woman might have no symptoms of Fabry disease, or have very mild symptoms. However, if the healthy X-chromosome is silenced in most cells, the woman will develop symptoms of Fabry disease.
What symptoms do women with Fabry disease develop?
Surveys of female patients indicate that most women with Fabry disease report symptoms of neuropathic pain and decreased quality of life. In addition, symptoms such as stroke may be more common in women with Fabry disease than in men.
Men with Fabry disease are prone to kidney problems, including kidney failure. This is less common in female patients, but can still occur.
Heart disease is common in female Fabry disease patients. Digestive problems, like vomiting, diarrhea, abdominal pain, and constipation occur in about 50–60% of patients.
Fabry disease in women also may have an effect on lifespan. However, it is difficult to say to what extent, given the rarity of the disease, and the fact doctors were not following disease progression or treating women with the disease for many years.
How do doctors treat Fabry disease in women?
There is no known cure for Fabry disease. However, there are treatments that can slow disease progression and improve patients’ quality of life.
Enzyme replacement therapy (ERT) is a treatment that supplies a form of the enzyme that patients are not able to make themselves. Researchers originally tested most ERTs for Fabry disease in male patients only. However, the treatment also can benefit women who have symptoms of the disease.
A small study testing the ERT Replagal (agalsidase alfa) demonstrated a similar response in female Fabry disease patients. Another study examined women with the disease who were being treated with Fabrazyme (agalsidase beta) for two years. Patients in the latter observational study were switched from Fabrazyme to Replagal for one year, and showed significant improvements in pain, quality of life, and cardiac and kidney function, indicating that their disease had stabilized with the change in treatment.
Last updated: June 26, 2020
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.
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