SEVERE COMBINED IMMUNODEFICIENCY DISEASE
This comprises a heterogeneous group of disorders characterized by severe cell-mediated and humoral immunodeficiency. Autosomal recessive and X- linked forms (the most common form in males) occur. Although infection is the most common cause of death, there is also an increased risk of lymphoma. Following the mapping of X-linked severe combined immunodeficiency disease to Xq13.1, mutations in the interleukin-2 receptor chain gene were identified (Noguchi et al. 1993; Puck et al. 1993). Mutations are heterogeneous and molecular genetic analysis is technically demanding (Puck et al. 1997, 1997). An atypical form is also recognized. At least eight autosomal genes are implicated in recessive SCID including adenosine deaminase, CD3 delta and CD3 epsilon chain, CD45, IL-7 receptor alpha chain, JAK3 and RAG1/RAG2 deficiencies, and Artemis mutations (Buckley 2004a, b). There is no evidence that heterozygotes for autosomal recessive causes of the disease (including adenosine deaminase deficiency) are at increased risk for cancer (Morrell et al. 1987). A recent Australian survey of SCID recorded an incidence of 1.8 per 100,000 births. Of 33 cases identified over a 6-year period, 26 were classical SCID and 7 were atypical. Of the classical cases, the causative genes/syndromes were IL2RG (n = 13), ADA (4), IL-7 receptor alpha chain (1), Omenn syndrome (2), and DiGeorge syndrome (2), and 4 were autosomal recessive, not otherwise defined (Yee et al. 2008).