HUMAN SEVERE COMBINED IMMUNODEFICIENCY - GENETIC, PHENOTYPIC, AND FUNCTIONAL DIVERSITY IN 108 INFANTS

Objective: To determine the relative frequencies of the different gene tic forms of severe combined immunodeficiency (SCID) and whether there are distinctive characteristics of the particular genotypes. Study de sign: The demographic, genetic, and immunologic features of 108 infant s with SCID who were treated consecutively at Duke University Medical Center were analyzed. Results: Eighty-nine subjects were boys and 19 w ere girls; there were 84 white infants, 16 black infants, and 8 Hispan ic infants, Forty-nine had X-linked SCID with mutations of common cyto kine receptor gamma chain (gamma(c)), 16 had adenosine deaminase (ADA) deficiency, 8 had Janus kinase 3 (Jak3) deficiency, 21 had unknown au tosomal recessive mutations, 1 had reticular dysgenesis, 1 had cartila ge hair hypoplasia, and 12 (all boys) had SCID of undetermined type, D eficiency of ADA caused the most profound lymphopenia; gamma(c) or Jak 3 deficiency resulted in the most B cells and fewest natural kilter (N K) cells; NK cells and function were highest in autosomal recessive an d unknown types of SCID.Conclusions: Different SCID genotypes are asso ciated with distinctive lymphocyte characteristics. The presence of NK function in ADA-deficient, autosomal recessive, and unknown type SCID s, and low NK function in a majority of gamma(c) and Jak3 SCIDs indica tes that some molecular lesions aff ect T, B, and NK cells (gamma(c) a nd Jak3), others primarily T cells (ADA deficiency), and others just T and B cells.