What is VEXAS syndrome?

VEXAS syndrome, which stands for “Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic,” is a rare and recently identified, chronically progressive autoinflammatory disorder. It was first described by Dr. Beck in a study published in the New England Journal of Medicine in 2020. The syndrome is associated with a somatic mutation in the UBA1 gene (see below). Before this study, the VEXAS syndrome is often misdiagnosed by hematologists, rheumatologists, and dermatologists due to the diverse and overlapping clinical manifestations.

Here are key characteristics and features of VEXAS syndrome:

1. Genetic Mutation: VEXAS syndrome is caused by a mutation in the UBA1 gene with the majority of mutations at codon41. This mutation is somatic, meaning it occurs in certain cells of the body but not in the germline (sperm or egg cells). The UBA1 gene is involved in ubiquitin activation, a process critical for regulating protein degradation. Although the UBA1 mutations in VEXAS is somatic, most of patients with the VEXAS syndrome is identified by Sanger sequencing, a less sensitive testing method. Although early detection is not required, it has been suggested that early detection may benefit patient monitoring and treatment if necessary.
2. Autoinflammatory Nature: VEXAS syndrome is characterized by autoinflammation caused by the immune system mistakenly attacking the body’s own tissues. This inflammation can affect various organs and tissues, contributing to the diverse clinical manifestations associated with the syndrome and difficult identification before 2020.
3. Clinical Features: Individuals with VEXAS syndrome may experience a range of symptoms, including fever, joint swelling, blood clots, vacuoles in myeloid cells, respiratory (coughing and shortness of breath) and gastrointestinal issues, and skin rashes that may be painful. As you can see, these symptoms can be quite varied involving multiple organs and may overlap with those of other inflammatory disorders such as MDS (Myelodysplastic Syndromes).
4. Adult Onset: VEXAS syndrome typically manifests in adulthood, often in middle age (often after 50). Although it often occurs to men (1 in 4,000), it happens to women as well (>6 fold less than men). With more and more people are diagnosed, the ratio may change. Without genetic testing, it can be challenging to diagnose due to its rarity and the diverse array of symptoms.
5. Diagnostic Challenges: Diagnosing VEXAS syndrome involves genetic testing to identify the somatic mutation in the UBA1 gene. The diagnosis is further complicated by the fact that the mutation is not present in all cells, making it necessary to analyze specific affected tissues.
6. Limited Treatment Options: Currently, there is no cure and treatment options for VEXAS syndrome are limited. Managing the condition often involves addressing specific symptoms, such as inflammation and blood clotting issues. Because VEXAS Syndrome patients are unlikely to improve with immunosuppressive drugs, other alternative therapies should be considered once the patients are diagnosed through genetic testing.
7. Shortened life expectancy: Although more studies are needed to determine the life expectancy of the patients with the VEXAS syndrome, early studies have shown that the mortality of the VEXAS-relapsed polychondritis (RP) patients is much greater than patients with RP alone.

Since the disease has been published, there are a great number of papers published globally and new information on the disease will continue to emerge.  If you know someone showing symptoms suggestive of VEXAS syndrome, it is crucial to consult with doctors for an accurate diagnosis and appropriate treatment management.

We currently provide research testing services and sell the UBA1 genetic testing kits for your research needs. We welcome academic collaborators to work with us. For more information about the product and service for the VEXAS Syndrome Testing, refer to our website and brochure.

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