Immunodeficiency 24D81.2

Immunodeficiency 24, IMD24 for short, is a very rare autosomal recessive immunodeficiency characterized by mutations in the CTPS1 gene (123860). The clinical picture is apparently characterized by a large phenotypic variability (Trück J et al. 2016).

Immunologically, an impairment of activated T and B cells is evident, which presents as a deficient proliferative capacity to antigen receptor-mediated activation. Patients develop severe chronic viral infections in early childhood. Causative agents are herpesviruses, including Epstein-Barr virus (Kucuk ZY et al. (2016) and varicella-zoster virus (VZV). Patients also suffer from recurrent bacterial infections, a spectrum typical of combined adaptive immunity deficiency (CID) (Martin et al. 2014).

Martin et al (2014) reported on 5 families with one or two affected children in the northwestern region of England who suffered from early-onset severe chronic viral infections caused mostly by herpesviruses, including EBV and VZV, and recurrent bacterial infections. 2 patients suffered from EBV-associated B-cell non-Hodgkin lymphoma. Overall, the clinical phenotype was severe, and 3 patients died. 6 of the 8 patients underwent hematopoietic stem cell transplantation.

Lab: Variable lymphopenia that converted to an inverse CD4/CD8 T-cell ratio (601083) during infectious episodes, whereas other hematologic values were usually normal. IgG levels were normal or elevated with elevated IgG but low IgG2 levels and low antibody titers to Streptococcus pneumoniae. Further analysis performed in one patient showed lymphopenia of naive CD4+ T cells, increased numbers of effector memory T cells, low numbers of CD27+ memory B cells, complete absence of both invariant T cell populations (iNKT and MAIT cells), and impaired PHA- and antigen-induced proliferation of peripheral blood mononuclear cells.

1. Kucuk ZY et al (2016) CTP Synthase 1 Deficiency in Successfully Transplanted Siblings with Combined Immune Deficiency and Chronic Active EBV Infection. J Clin Immunol 36:750-753.
2. Martin E et al.(2014) CTP synthase 1 deficiency in humans reveals its central role in lymphocyte proliferation. Nature 510: 288-292.
3. Trück J et al. (2016) Variable phenotype and discrete alterations of immune phenotypes in CTP synthase 1 deficiency: Report of 2 siblings. J Allergy Clin Immunol 138: 1722-1725.