Novel approach to the evaluation of primary immunodeficiencies

Primary immunodeficiency diseases usually manifest early in infancy and childhood, but some manifest later in life. The skin and the gastrointestinal (GI) and sinopulmonary tracts are major sites of involvement, since they interface with the environment. These diseases are a result of heritable genetic defects that are usually recessive conditions, and frequently located on the X chromosome, hence a male predominance. Clinical manifestations are recurrent and severe deep infections in the skin or GI or sinopulmonary tract that require intravenous antibiotics, as well as infections with opportunistic organisms (for example, Giardia lamblia). The major causes of the primary immunodeficiency diseases include B-lymphocyte disorders, T-lymphocyte disorders, combined B- and T-cell disorders, as well as unconventional disorders such as interleukin-1 receptor-associated kinase 4 (IRAK-4) deficiency and warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis (WHIM) syndrome (CXCR4 deficiency). Early diagnosis is critical to effectively manage these conditions in the afflicted patients and to identify disease gene carriers for genetic counseling.