TCRa deficiency

Gene: TRAC

Inheritance pattern: Autosomal recessive

This is an autosomal recessive disease due to mutation in the TCR alpha subunit constant (TRAC) gene that causes markedly reduced surface expression of the T cell receptor alpha-beta (TCRalpha-beta) complex. Such a complex is crucial for T cell signaling and function. Those affected have absent numbers of TCR-alpha-beta+ T cells but increased TCR-gamma-delta+ T cells together with hypereosinophilia, 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 Herpesviridae 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.