WEDNESDAY, Jan. 25, 2023 (HealthDay News) -- The prevalence and clinical manifestations of UBA1 variants associated with VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome have been identified in a single health system, according to a study published in the Jan. 24/31 issue of the Journal of the American Medical Association.
David B. Beck, M.D., Ph.D., from the National Institutes of Health in Bethesda, Maryland, and colleagues conducted a retrospective observational study involving 163,096 participants within the Geisinger MyCode Community Health Initiative to examine the prevalence of pathogenic variants in UBA1.
The researchers found that 11 of the participants harbored likely somatic variants at known pathogenic UBA1 positions; all 11 had clinical manifestations consistent with VEXAS syndrome. Five individuals (45 percent) did not meet the criteria for rheumatologic and/or hematologic diagnoses previously associated with VEXAS syndrome, but all 11 had anemia, which was macrocytic in 10 individuals, with concomitant thrombocytopenia in 10 individuals. Of the 11 patients identified, one male patient had a pathogenic variant identified prior to onset of VEXAS-related signs or symptoms; disease with heterozygous variants occurred in two female patients. One symptomatic patient had a previously unreported UBA1 variant, with in vitro data supporting a catalytic defect and pathogenicity. Disease-causing UBA1 variants were identified in one of 13,591 unrelated individuals and in one of 4,269 men and one in 26,238 women aged older than 50 years.
"Now that we know VEXAS syndrome is more common than many other types of rheumatologic conditions, physicians need to add this condition to their list of potential diagnoses when confronted by patients with persistent and unexplained inflammation and low blood cell counts, or anemia," Beck said in a statement.