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")
Subscribers log in hereLiterature review current through: Nov 2017. | This topic last updated: Sep 15, 2017.References
- Picard C, Al-Herz W, Bousfiha A, et al. Primary Immunodeficiency Diseases: an Update on the Classification from the International Union of Immunological Societies Expert Committee for Primary Immunodeficiency 2015. J Clin Immunol 2015; 35:696.
- Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol 2015; 136:1186.
- Cirillo E, Giardino G, Gallo V, et al. Severe combined immunodeficiency--an update. Ann N Y Acad Sci 2015; 1356:90.
- Griffith LM, Cowan MJ, Notarangelo LD, et al. Primary Immune Deficiency Treatment Consortium (PIDTC) update. J Allergy Clin Immunol 2016; 138:375.
- van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM. TREC Based Newborn Screening for Severe Combined Immunodeficiency Disease: A Systematic Review. J Clin Immunol 2015; 35:416.
- Roifman CM, Zhang J, Chitayat D, Sharfe N. A partial deficiency of interleukin-7R alpha is sufficient to abrogate T-cell development and cause severe combined immunodeficiency. Blood 2000; 96:2803.
- Puel A, Leonard WJ. Mutations in the gene for the IL-7 receptor result in T(-)B(+)NK(+) severe combined immunodeficiency disease. Curr Opin Immunol 2000; 12:468.
- Puel A, Ziegler SF, Buckley RH, Leonard WJ. Defective IL7R expression in T(-)B(+)NK(+) severe combined immunodeficiency. Nat Genet 1998; 20:394.
- Villa A, Notarangelo LD, Roifman CM. Omenn syndrome: inflammation in leaky severe combined immunodeficiency. J Allergy Clin Immunol 2008; 122:1082.
- Shiow LR, Roadcap DW, Paris K, et al. The actin regulator coronin 1A is mutant in a thymic egress-deficient mouse strain and in a patient with severe combined immunodeficiency. Nat Immunol 2008; 9:1307.
- Kung C, Pingel JT, Heikinheimo M, et al. Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease. Nat Med 2000; 6:343.
- Tchilian EZ, Wallace DL, Wells RS, et al. A deletion in the gene encoding the CD45 antigen in a patient with SCID. J Immunol 2001; 166:1308.
- Roberts JL, Buckley RH, Luo B, et al. CD45-deficient severe combined immunodeficiency caused by uniparental disomy. Proc Natl Acad Sci U S A 2012; 109:10456.
- Punwani D, Zhang Y, Yu J, et al. Multisystem Anomalies in Severe Combined Immunodeficiency with Mutant BCL11B. N Engl J Med 2016; 375:2165.
- Keller MD, Ganesh J, Heltzer M, et al. Severe combined immunodeficiency resulting from mutations in MTHFD1. Pediatrics 2013; 131:e629.
- Watkins D, Schwartzentruber JA, Ganesh J, et al. Novel inborn error of folate metabolism: identification by exome capture and sequencing of mutations in the MTHFD1 gene in a single proband. J Med Genet 2011; 48:590.
- 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