Understanding Fabry disease

Patient Voice spoke with Vancouver-based medical geneticist Dr. Anna Lehman to learn about Fabry disease, what symptoms to watch for, and when to get tested.

Submitted by Dr. Anna Lehman.

Fabry disease is a rare disorder that can be passed down from generation to generation. Although it can be difficult to diagnose, early detection is the key to treating this life-altering — and in many cases life-threatening — disorder.

We met with Dr. Lehman to learn more about this genetic condition. Dr. Lehman is Medical Director of the Adult Metabolic Diseases Clinic at Vancouver General Hospital and an Associate Professor of Medical Genetics at the University of British Columbia.

1. What is Fabry disease? 

Fabry disease is an inherited disorder that causes damaging build-up of glycolipids in cells and organ tissues. Glycolipids are large molecules that form a necessary part of the cell membrane. They're usually recycled by an enzyme called α‐galactosidase A, also known as α‐Gal A. But in people with Fabry disease, there is either an ineffective version of the enzyme, not enough of it, or it’s missing altogether, so glycolipids don’t get adequately recycled and build up, particularly in small blood vessels, the heart, and the kidneys. Over time, that build-up causes organ dysfunction such as an irregular heartbeat, heart failure, or kidney failure. 

Fabry disease often slides under the radar because its early symptoms, such as pain, fatigue, and gastrointestinal issues, can easily be mistaken for more common conditions like irritable bowel syndrome or fibromyalgia.

2. Who does Fabry disease affect?

Fabry disease can affect people of all ages, backgrounds, and ethnicities. It occurs in both men and women, and it’s estimated to affect at least one in every 40,000 to 60,000 people. 

Fabry disease tends to affect men more severely than women because the dysfunctional gene that causes Fabry is located on the X chromosome, which determines sex. Female patients with Fabry disease have two X chromosomes, giving them both a normal working copy of the alpha-gal A gene as well as a copy of the dysfunctional gene. In contrast, male patients with Fabry disease only have one X chromosome, and therefore have only a copy of the gene for dysfunctional alpha-gal enzyme. 

While symptoms of the disease can be similar in men as in women, female patients tend to get diagnosed later.

Most people with the gene for Fabry disease will be affected eventually, whether male or female. The disease has a wide range of severity, with some being affected in childhood and others not until late in life.

“If Fabry is treated at an early stage, it’s possible to significantly slow down disease progression.”

3. How does Fabry disease typically present?
Fabry disease often presents first with episodes of burning pain in the hands and feet, although this isn’t always what leads to a diagnosis. 

If Fabry disease hasn’t already been diagnosed in a family, it can take many years to identify. For example, a person might be having episodes of burning pain in their hands and feet. They may also have gastrointestinal issues causing bloating and pain, or occasional heart palpitations. But individually, these symptoms may not lead the person to seek medical attention, or may not provide enough direct clues for a doctor to think to test for this very rare condition. 

We often see patients who had been having symptoms for decades before the right test was done because of more advanced disease. Usually, a Fabry diagnosis will happen after there has already been damage to the kidneys, which might be noticed during a routine blood or urine test, or the heart, causing symptoms such as shortness of breath, chest pain, or palpitations. 

Even within families with a history of Fabry disease, there’s a lot of variability among individuals.

4. How is Fabry disease diagnosed?

Fabry disease is best confirmed with a genetic test because other tests can sometimes miss it in female patients. For example, while there's a way to directly measure the enzyme affected by Fabry disease, results of this test can sometimes appear normal in female patients who are in fact severely affected. Genetic tests aren’t invasive; they can generally be done on a simple blood sample or even a saliva sample.

Dr. Lehman has dedicated her research to identifying the genetic causes for rare diseases.

5. Why is it important to get tested if Fabry disease runs in your family?

This disease can be passed down for many, many generations in a family. In Canada, Fabry disease in one family in Nova Scotia has been traced back to a single ancestor who immigrated in the 1750s. Her lineage has resulted in Nova Scotia having a much higher rate of Fabry disease than other provinces. 

There is treatment available that is most effective when started in the early stages of organ damage, which may be before a person even realizes they have a problem. If Fabry is treated at an early stage, it’s possible to significantly slow down disease progression. 

6.What would you say to patients’ family members who are fearful of genetic testing?

Making the decision to get tested can be very personal. Some people will want to wait until "a good time," so to speak. It can be tricky to predict how a new diagnosis could impact insurability, for example, despite some protective legislation recently passed in Canada. Others will want to know their status right away, not wanting to risk missing the period when treatment can be most effective. And for those planning families, learning whether the disease could be passed on is a priority. 

Anyone with a family history of Fabry disease should speak with a physician or genetic counsellor about their personal situation.

If you’ve been diagnosed with Fabry disease, either recently or in the past, there's a community of patients, caregivers, and clinicians here to support you. To learn more about Fabry, seek support, or access additional resources, please connect with the Canadian Fabry Association.  

This initiative was supported by Chiesi Global Rare Diseases. The content was developed by Patient Voice, and the supporter did not influence the final article or editorial themes.