A new program embedded within the rheumatology service provides genetic evaluations of patients with atypical autoinflammatory disease manifestations. The program builds on pioneering research findings that point to common genetic underpinnings across certain rheumatic conditions.

“When we can provide a molecular diagnosis that may reclassify patients, it’s going to be even more beneficial for figuring out exactly how to treat them.”

David B. Beck, MD, PhD

“Clinical diagnoses are helpful, but when we can provide a molecular diagnosis that may reclassify patients, it’s going to be even more beneficial for figuring out exactly how to treat them,” says David B. Beck, MD, PhD, an assistant professor in the Center for Human Genetics and Genomics.

Dr. Beck joined the faculty in 2021 and launched the Inflammatory Disease Genetics Program a few months later. While Dr. Beck is leading the genetic evaluations, genetic counselor Anna Cantor, MA, MS, works with patients and their families to understand the testing procedure, its implications for their care, and the potential genetic risk to other relatives.

The program is accepting referrals of patients whose inflammatory conditions have not responded well to treatment, or for those with unusual clinical presentations.

New Options for Vexing VEXAS

As a complement to his clinical work, Dr. Beck’s research uses cellular and animal models to explore the genetic and molecular underpinnings of rheumatic diseases with unexplained inflammation.

Among adult patients, for example, recent research has underscored the importance of somatic mutations in driving age-related diseases.

In a groundbreaking 2020 New England Journal of Medicine study, Dr. Beck and colleagues reported that somatic mutations in the UBA1 gene on chromosome X cause VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, seen almost exclusively in male patients. In 2021, the American Society of Hematology named the research group’s new disease discovery “This Year’s Best in Hematology Diagnosis.”

Many of the patients in the study were previously given different rheumatic and hematologic diagnoses, such as relapsing polychondritis or myelodysplastic syndrome, but carried the same genetic mutation.

“It shows that these seemingly different diseases have the same underlying etiology,” Dr. Beck says. “Secondly, it helps us understand that in some cases, the clinical diagnosis isn’t anywhere near as helpful as the genetic diagnosis.”

Leveraging the information from the genetic evaluation has guided clinicians toward more effective VEXAS syndrome therapies such as bone marrow transplants, Dr. Beck explains.

Expanding Genetics-Driven Insights

Dr. Beck envisions that genetic evaluations will open up new diagnostic and therapeutic options for many atypical conditions.

“You can take patients out of these undiagnosed categories and give them a very highly specific diagnosis, which can have big prognostic and treatment implications,” he says.

The Center for Human Genetics & Genomics has placed a growing emphasis on integrating genetics-driven personalized medicine into medical specialties. Given NYU Langone Health’s robust clinical practice in rheumatology, Dr. Beck says, it made sense to merge that strength with the medical center’s unique genetics infrastructure.

“This is pairing the best of both worlds,” he says.