TCRa deficiency
Related gene: TRAC
Inheritance pattern: Autosomal recessive
This is an autosomal recessive disease due to variants in the TCR alpha subunit constant (TRAC) gene that causes markedly reduced surface expression of the T cell receptor alpha-beta (TCRalpha-beta) complex. The TCRalpha-beta complex is crucial for T cell signaling and function.
Those with TCRa deficiency have absent numbers of TCR-alpha-beta+ T cells but increased TCR-gamma-delta+ T cells together with high numbers of eosinophils, and sometimes elevated immunoglobulin E (IgE) but normal IgG levels. Patients present within the first two years of life suffering from recurrent respiratory tract infections, candidiasis, and gastroenteritis (Salmonella, Cryptosporidium, rotavirus) that respond to conventional treatment. Susceptibility to herpesvirus infections is also reported. Additional clinical features included failure to thrive, immune dysregulation (e.g., vitiligo, alopecia, eczema, and autoimmune hemolytic anemia), lymphadenopathy, and hepatomegaly. Hematopoietic stem cell transplantation (HSCT) has been curative in this disease.
