CD3G deficiency
Related gene: CD3G
Inheritance pattern: Autosomal recessive
CD3 chains are important components of the TCR/CD3 complex and have a crucial role in T cell signaling and function. While CD3 delta, CD3 epsilon, or CD3 zeta deficiencies lead to a severe combined immunodeficiency (SCID) phenotype with absent T cells and present but non-functional B cells, individuals with CD3G deficiency have residual T cell function and numbers, and a broad spectrum of clinical phenotypes ranging from immune deficiency to immune dysregulation with autoimmunity.
The onset for individuals with CD3G deficiency is usually delayed, in childhood and young adulthood; however, a few have been reported with early onset SCID phenotype. Features include recurrent lung and urinary tract infections, intractable diarrhea, and failure to thrive. Chronic cytomegalovirus (CMV) infection has also been reported. Multiple autoimmune phenomena can occur, including autoimmune cytopenias, autoantibody positive severe colitis, cardiomyopathy, thyroiditis, nephritis, alopecia, and vitiligo. Laboratory data show T cell lymphopenia with low TCR-alpha-beta expression and CD3 on T cells, low immunoglobulin (Ig), and poor vaccination responses. Ig replacement therapy with antimicrobial and immunosuppressive therapy are supportive measures; however, in the most severe cases, hematopoietic stem cell transplantation (HSCT) is required.
