A great study of a recently described rheumatologic/hematologic disorder VEXAS (vacuoles, E1-ubiquitin-activating enzyme, X-linked, autoinflammatory, somatic) syndrome recently appeared in JAMA, describing the frequency and presentations of UBA1 variant.
This retrospective study evaluated the frequency of UBA1 variants in exome data from 163 096 participants within the Geisinger MyCode Community Health Initiative. Overall they genotypically identified 11 individuals (1 in 13 591) with the UBA1 disease-causing variant. The clinical presentations were determined from electronic health record data (1996 to 2022).
The population cohort was 61% female, 94% white with a mean age of 52.8 years. The 11 individuals (9 male, 2 female) with UBA1 variants had manifestations consistent with VEXAS syndrome . Nearly half (5/11 -45%) did not meet previously proposed VEXAS criteria. Yet all of them had anemia (11/11) (hemoglobin: mean, 7.8 g/dL) that was macrocytic in 91%) and associated with thrombocytopenia (10/11 [91%])
This exome study cohort showed the prevalence of disease-causing UBA1 variants to be 1 in 13 591 unrelated individuals; more so in men (1/4269) older than 50 years, but less in women (1/26 238) over 50 years.
These data are from a single regional health system in northeastern US. Additional studies are needed in unselected and genetically diverse populations to better define the prevalence and phenotypic spectrum of the VEXAS syndrome.