Severe combined immunodeficiency (SCID) is a fatal primary immune condition characterized by the absence of both humoral and cellular immunity with severe lymphopenia. Patients with SCID have reduced numbers and function of both T and B lymphocytes (and in some cases, natural killer [NK] cells) and hypogammaglobulinemia. If left untreated, babies with SCID most often die within 1 to 2 years of life because of severe, recurrent infections.
Since SCID was initially described over 50 years ago, 15 specific genetic mutations that contribute to disease development have been identified. The most common type is X-linked SCID (SCID-X1), which accounts for approximately 46% of cases in the United States (Figure 111-1). SCID can also be inherited as an autosomal recessive disease that results from deficiencies in adenosine deaminase (ADA), Janus kinase 3 (JAK3), interleukin 7 receptor α chain (IL7R), recombination activating genes (RAG1 or RAG2), Artemis gene, CD45, and others (Table 111-1).
Table 111-1Classification of Severe Combined Immunodeficiency (SCID) ||Download (.pdf) Table 111-1Classification of Severe Combined Immunodeficiency (SCID)
|Lymphocyte Profile ||Disease ||Genetic Mutation ||Inheritance ||Chromosome Band |
|T Cells ||B Cells ||Natural Killer (NK) Cells |
|– ||– ||– ||Adenosine deaminase deficiency ||Adenosine deaminase (ADA) ||AR ||20q13.2-q13.11 |
|– ||– ||– ||Reticular digenesis ||AK2 ||AR ||1q35 |
|– ||– ||+ ||Artemis gene deficiency ||Artemis gene (DCLRE1C) ||AR ||10p13 |
|– ||– ||+ ||Omenn syndrome ||RAG1 or RAG2 ||AR ||11p13.41 |
|– ||– ||+ ||DNA protein kinase catalytic subunit (DNA-PKcs) ||PRKDC ||AR ||8q11 |
|– ||+ ||– ||X-linked SCID ||Common γ chain receptor (IL-2Rg) ||XL ||Xq13.1 |
|– ||+ ||– ||JAK3 deficiency ||JAK3 ||AR ||19q13.1 |
|– ||+ ||+ ||Interleukin (IL) 7 α-chain receptor deficiency ||Interleukin (IL) 7 α-chain receptor (CD127) ||AR ||5p13 |
|– ||+ ||+ ||CD3 deficiency ||CD3δ, CD3ε, or CD Ζ ||AR ||11q23 |
|– ||+ ||+ ||Actin-regulating protein coronin 1A (CORO1A) deficiency ||CORO1A ||AR ||16p11 |
|CD45– ||+ ||+ ||CD45 deficiency ||CD45 tyrosine phosphatase (PTPRC) ||AR ||1q31 |
|CD4+ ||+ ||+ ||ZAP70 kinase deficiency ||ZAP70 tyrosine kinase ||AR ||2q12 |
|CD8+ ||+ ||+ ||p56lck deficiency ||p56lck ||AR ||1p35 |
|CD8+ ||B+DR ||+ ||Major histocompatibility complex (MHC) II deficiency ||RFXAP CIITA RFXANK RFX5 || |
The relative frequencies of particular genetic mutations were evaluated in 174 consecutive cases of human severe combined immunodeficiency (SCID) evaluated at Duke University over 30 years. The most common type is X-linked SCID, which disables common gamma (γc) signaling. ADA, adenosine deaminase; JAK3, Janus kinase 3; IL7R, interleukin 7 receptor α chain; RAG1 or RAG2, recombination activating genes 1 or 2. (Reproduced with permission ...