Severe combined immunodeficiency (SCID): Specific defects
- Francisco A Bonilla, MD, PhD
Francisco A Bonilla, MD, PhD
- Section Editor — Immunology and Immunodeficiency
- Associate Professor of Pediatrics
- Harvard Medical School
Combined immunodeficiency syndromes are a heterogeneous group of disorders arising from a disturbance in the development and function of both T and B cell (cellular and humoral immunity) arms of the adaptive immune system (figure 1 and table 1 and table 2) [1,2]. These disorders are termed "severe" (eg, severe combined immune deficiency [SCID]) when they lead to early death from overwhelming infection, typically in the first year of life [3-5]. Mutations of a particular gene may lead to SCID or to milder immunodeficiency, depending upon whether the defect is complete or partial. Gene defects that lead to partial function of the gene product are called "hypomorphic", whereas complete defects are called "null" or "amorphic."
Brief synopses are given for the molecular types of SCID that are discussed in detail separately:
●X-linked SCID (see "X-linked severe combined immunodeficiency (SCID)")
●Adenosine deaminase (ADA) deficiency (see "Adenosine deaminase deficiency: Pathogenesis, clinical manifestations, and diagnosis")
●Artemis, recombinase activating gene (RAG)-1, RAG-2, and DNA protein kinase catalytic subunit (DNA-PKcs) deficiencies (see "T-B-NK+ SCID: Pathogenesis and genetics")
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- T-B+NK+ SCID
- Interleukin-7 receptor alpha chain (CD127) deficiency
- Actin-regulating protein coronin 1A deficiency
- CD45 deficiency
- CD3 complex component deficiencies
- B cell chronic lymphocytic leukemia/lymphoma 11B (BCL11B) defect
- T-B+NK- SCID
- X-linked SCID
- JAK3 deficiency
- T-B-NK+ SCID
- T-B-NK- SCID
- Adenosine deaminase deficiency
- Reticular dysgenesis
- MTHFD1 deficiency