Novel Primary Immunodeficiencies

In the last 10 years, new primary immunodeficiencies have been identified that provide a molecular explanation for severe pediatric infections previously thought to be idiopathic. These new hereditary immunodeficiencies are associated with severe and/or recurrent infections caused by a single family of microorganisms, in contrast to what is observed in “classic” primary immunodeficiency (Notarangelo L et al., 2004). Standard immunologic explorations such as white blood counts, lymphocyte counts, vaccine serology, immunoglobulin levels, and complement were normal. However, the affected children were susceptible to infection by a single type of microorganism, and such infections were in some cases fatal. The aim of this chapter is to describe few new syndromes involving genetic predisposition to infectious diseases: IL-12-IFNγ axis deficiency (Mendelian susceptibility to mycobacterial disease), STAT-1 deficiency (predisposition to mycobacterial and viral diseases) and NEMO, IκBα and IRAK-4 deficiencies (predisposition to infections caused by pyogenic bacteria) (Table 6.1).