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Home Lifestyle Health

Newly Discovered Genetic Disease Is More Common Than Expected

ALY by ALY
January 25, 2023
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Jan. 25, 2023 – A recently discovered inflammatory disease known as VEXAS syndrome is more widespread and dangerous than previously understood, a new genetic analysis suggests. While it’s rare, researchers believe the disease may affect tens of thousands of men in the U.S. and may frequently go undiagnosed.

“Is VEXAS really more common than we think with patients hiding in plain sight? The answer is yes,” says Mayo Clinic rheumatologist Matthew J. Koster, MD, who’s studied the disease but didn’t take part in the new research project. His institution, he says, sees a patient with the disease every week or two. 

Researchers first described VEXAS syndrome in 2020 and gave it its name, which stands for several of its traits – vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic. The disease is linked to a gene mutation that seems to disrupt how the body identifies dysfunctional proteins so they can be eliminated.

“The disease is quite severe,” says study lead author David Beck, MD, PhD, an assistant professor in the Department of Medicine at NYU Langone Health. 

Patients with the condition “have a variety of clinical symptoms affecting different parts of the body and are being managed by different medical specialties.”

Symptoms can include anemia – a low level of red blood cells in the body – and inflammation that affects the skin, lungs, bone, cartilage, and joints. “These symptoms are frequently mistaken for other rheumatic or hematologic [blood] diseases,” Beck says. “However, this syndrome has a different cause, is treated differently, requires additional monitoring, and can be far more severe.”

According to Beck, who helped discover the disease, hundreds of people have been diagnosed with VEXAS syndrome in the short time since it was defined. The disease is believed to be fatal in some cases. 

For the new study, researchers looked for relevant variants in genetic data from 163,096 people (average age 52.8 years; 94% white; 61% women) who were patients at 10 Pennsylvania hospitals from 1996 to 2022.

Eleven people (nine male, two female) had the likely variants, and all had anemia. 

Just over half of the patients – 55% – had a clinical diagnosis that was previously linked to VEXAS syndrome. “This means that slightly less than half of the patients had no clear associated clinical diagnosis,” Beck says. “VEXAS syndrome represents an example of a multi-system disease where patients and their symptoms may get lost in the shuffle.”

Moving forward, he says, doctors should be on the lookout for patients with unexplained inflammation and various symptoms who can’t be diagnosed or don’t respond to their first treatments. “These patients will also frequently be anemic, have low platelet counts and elevated markers of inflammation in the blood, and be dependent on corticosteroids,” which dampen the immune system, he says.    

Koster says the disease is so common that “clinicians should consider that some of the patients with diseases that are not responding to treatment may in fact have VEXAS.” 

Diagnosis of VEXAS can be made via genetic testing.

As for treatment, Beck says the disease can be partly controlled by medications that aim to tame the immune system. Also, he says, bone marrow transplants have shown signs of being effective. 

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