Severe combined immunodeficiency

Severe combined immunodeficiency
ICD-10	D81.0-D81.2
ICD-9	279.2
DiseasesDB	11978
eMedicine	med/2214
MeSH	D016511

Template:Search infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Mohsen Basiri M.D.

Classification

Previous classification system for SCID was based upon the presence of molecular defects affecting T cell numbers and presence or absence of defects affecting B and/or NK cell numbers, and SCID syndromes were classified as T-B+NK+, T-B+NK-, T-B-NK+, or T-B-NK- regardless of the functional status of these cells, since genetic diagnosis was more difficult to establish meanwhile, the mutated genes responsible for the majority of patients with SCID are known and can be readily defined. Then, it is more acceptable to classify SCID based upon the particular molecular defect once it is detected, especially the genotype can affect treatment methods and mesuarments for post treatment complications.

Beyond this phenotypic classification

Type	Gene defects	Description
X-linked severe combined immunodeficiency	IL-2R common gamma chain	IL2RG is a protein that is shared by the receptors for interleukins IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. These interleukins and their receptors are involved in the development and differentiation of T and B cells. mutations cause widespread defects in interleukin signalling. The result is a near complete failure of the immune system to develop and function, with low or absent T cells and NK cells and non-functional B cells. IL2RG is encoded on the X chromosome; therefore, this variant of SCID is X-linked, and account for approximately 50% of all patients with SCID.
Janus-associated kinase 3 deficiency (T– B+NK–)	Janus kinase 3	JAK3 is a protein tyrosine kinase (PTK) that associates with the common γ chain of the IL receptors. Deficiency of this protein results in the same clinical manifestations as those of XL-SCID.
Adenosine deaminase deficiency	ADA	ADA deficiency accounts for 20% of all SCID cases. Adenosine deaminase (ADA), is necessary for the breakdown of purines. Lack of ADA leads to the accumulation of intermediate dATP, which results in lymphocyte toxicity,particularly with immature thymic lymphocytes, then lymphocyte proliferation is inhibited and the immune system is compromised.
Bare lymphocyte syndrome	gene regulating expression of MHC type II	Bare lymphocyte syndrome is a deficiency of major histocompatibility complex (MHC). MHC type II is decreased on mononuclear cells. MHC type I levels may be decreased or absent entirely. The defect occurs in a gene regulating expression of MHC type II
ζ chain–associated protein (ZAP)-70 deficiency	Tyrosine kinase	Due to mutation in the gene coding for throsine kinase, which is important in T-cell signaling and is t icritical in positive and negative selection of T cells in the thymus

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Reticular dysgenesis	Adenylate kinase 2	Reticular dysgenesis is a rare variant of SCID arising from the inability of granulocyte precursors to form granules secondary to mitochondrial adenylate kinase 2 malfunction.
IL-7R α chain deficiency	IL-7RA
Deficiency of the recombination-activating genes RAG1 and RAG2 (T– B– NK+)	RAG1/RAG2
Ligase 4 deficiency (T– B– NK+)
CD45 deficiency
Omenn syndrome		The manufacture of immunoglobulins requires recombinase enzymes derived from the recombination activating genes RAG-1 and RAG-2. These enzymes are involved in the first stage of V(D)J recombination, the process by which segments of a B cell or T cell's DNA are rearranged to create a new T cell receptor or B cell receptor (and, in the B cell's case, the template for antibodies). Certain mutations of the RAG-1 or RAG-2 genes prevent V(D)J recombination, causing SCID.
Artemis/DCLRE1C	DCLRE1C	An enzyme that opens DNA hairpin during variable diversity joining [VDJ] rearrangement and RAG1 and RAG2 deficiencies

External links

• Learning About Severe Combined Immunodeficiency (SCID) NIH
• Buckley RH (2004). "Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution". Annu Rev Immunol. 22: 625–55. doi:10.1146/annurev.immunol.22.012703.104614. PMID 15032591.
• Chinen J, Puck JM (2004). "Successes and risks of gene therapy in primary immunodeficiencies". J Allergy Clin Immunol. 113 (4): 595–603, quiz 604. doi:10.1016/j.jaci.2004.01.765. PMID 15100660.
• Church AC (2002). "X-linked severe combined immunodeficiency". Hosp Med. 63 (11): 676–80. PMID 12474613.
• Gennery AR, Cant AJ (2001). "Diagnosis of severe combined immunodeficiency". J Clin Pathol. 54 (3): 191–5. doi:10.1136/jcp.54.3.191. PMID 11253129.
• Concept of gene therapy for SCID