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Complement component 2 deficiency(C2D)

MedGen UID:
461625
Concept ID:
C3150275
Disease or Syndrome
Synonyms: C2 deficiency; C2D; Complement Component C2 Deficiency
 
Gene (location): C2 (6p21.33)
 
Monarch Initiative: MONDO:0009006
OMIM®: 217000

Definition

The complement system is a set of plasma proteins that serves as an effector of several biologic functions associated with inflammation, immunoregulation, and cytotoxicity. Deficiency of complement component-2 (C2D) is the most common defect of the complement system in persons of western European descent. In type I C2 deficiency, no C2 protein is translated; in type II, there is a selective block in C2 secretion. More than half of individuals with homozygous C2 deficiency have rheumatologic disorders such as systemic lupus erythematosus, Henoch-Schonlein purpura, or polymyositis. Other individuals experience recurrent pyogenic infections, and some C2-deficient individuals are asymptomatic (summary by Johnson et al., 1992, Wetsel et al., 1996). [from OMIM]

Additional description

From MedlinePlus Genetics
Complement component 2 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria and viruses. People with complement component 2 deficiency have a significantly increased risk of recurrent bacterial infections, specifically of the lungs (pneumonia), the membrane covering the brain and spinal cord (meningitis), and the blood (sepsis), which may be life-threatening. These infections most commonly occur in infancy and childhood and become less frequent in adolescence and adulthood.

Complement component 2 deficiency is also associated with an increased risk of developing autoimmune disorders such as systemic lupus erythematosus (SLE) or vasculitis. Autoimmune disorders occur when the immune system malfunctions and attacks the body's tissues and organs. Between 10 and 20 percent of individuals with complement component 2 deficiency develop SLE. Females with complement component 2 deficiency are more likely to have SLE than affected males, but this is also true of SLE in the general population.

The severity of complement component 2 deficiency varies widely. While some affected individuals experience recurrent infections and other immune system difficulties, others do not have any health problems related to the disorder.  https://medlineplus.gov/genetics/condition/complement-component-2-deficiency

Clinical features

From HPO
Systemic lupus erythematosus
MedGen UID:
6146
Concept ID:
C0024141
Disease or Syndrome
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by production of autoantibodies against nuclear, cytoplasmic, and cell surface molecules that transcend organ-specific boundaries. Tissue deposition of antibodies or immune complexes induces inflammation and subsequent injury of multiple organs and finally results in clinical manifestations of SLE, including glomerulonephritis, dermatitis, thrombosis, vasculitis, seizures, and arthritis. Evidence strongly suggests the involvement of genetic components in SLE susceptibility (summary by Oishi et al., 2008). Genetic Heterogeneity of Systemic Lupus Erythematosus An autosomal recessive form of systemic lupus erythematosus (SLEB16; 614420) is caused by mutation in the DNASE1L3 gene (602244) on chromosome 3p14.3. An X-linked dominant form of SLE (SLEB17; 301080) is caused by heterozygous mutation in the TLR7 gene (300365) on chromosome Xp22. See MAPPING and MOLECULAR GENETICS sections for a discussion of genetic heterogeneity of susceptibility to SLE.
Purpura
MedGen UID:
19584
Concept ID:
C0034150
Disease or Syndrome
Purpura (from Latin

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVComplement component 2 deficiency

Professional guidelines

PubMed

Turley AJ, Gathmann B, Bangs C, Bradbury M, Seneviratne S, Gonzalez-Granado LI, Hackett S, Kutukculer N, Alachkar H, Hambleton S, Ritterbusch H, Kralickova P, Marodi L, Seidel MG, Dueckers G, Roesler J, Huissoon A, Baxendale H, Litzman J, Arkwright PD
J Clin Immunol 2015 Feb;35(2):199-205. Epub 2015 Feb 8 doi: 10.1007/s10875-015-0137-5. PMID: 25663093
Middleton O, Cosimo E, Dobbin E, McCaig AM, Clarke C, Brant AM, Leach MT, Michie AM, Wheadon H
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Recent clinical studies

Etiology

Nagaraja V, Stewart TE, Mackay SG, Glenn DW, Wakefield D, Boutlis CS
Laryngoscope 2015 Apr;125(4):852-5. Epub 2014 Aug 14 doi: 10.1002/lary.24874. PMID: 25124395
Sullivan KE
Curr Opin Pediatr 1998 Dec;10(6):600-6. doi: 10.1097/00008480-199810060-00011. PMID: 9848020
Sim E
Complement Inflamm 1989;6(2):119-26. doi: 10.1159/000463084. PMID: 2524348
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Diagnosis

McMurray JC, Schornack BJ, Weskamp AL, Park KJ, Pollock JD, Day WG, Brockshus AT, Beakes DE, Schwartz DJ, Mikita CP, Pittman LM
Allergy Asthma Proc 2024 Sep 1;45(5):305-309. doi: 10.2500/aap.2024.45.240050. PMID: 39294906Free PMC Article
Jara LJ, Navarro C, Medina G, Vera-Lastra O, Saavedra MA
Curr Rheumatol Rep 2009 Dec;11(6):410-5. doi: 10.1007/s11926-009-0060-y. PMID: 19922730
Sim E
Complement Inflamm 1989;6(2):119-26. doi: 10.1159/000463084. PMID: 2524348
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Maddison PJ
Clin Rheum Dis 1982 Apr;8(1):105-19. PMID: 6749392

Therapy

Kaplan AP
Chem Immunol Allergy 2014;100:140-7. Epub 2014 May 22 doi: 10.1159/000358619. PMID: 24925394
Hauck F, Lee-kirsch MA, Aust D, Roesler J, Pessler F
Arthritis Care Res (Hoboken) 2011 Mar;63(3):454-9. doi: 10.1002/acr.20361. PMID: 20890976
Sim E
Complement Inflamm 1989;6(2):119-26. doi: 10.1159/000463084. PMID: 2524348
Farnam J, Grant JA
Dermatol Clin 1985 Jan;3(1):85-95. PMID: 2868818
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Clin Rheum Dis 1982 Apr;8(1):29-47. PMID: 6288318

Prognosis

Oprea Y, Antohi DR, Vague M, Delbourgo Patton C, Wu B, Ortega-Loayza AG
Am J Clin Dermatol 2024 Sep;25(5):701-716. Epub 2024 Jul 1 doi: 10.1007/s40257-024-00875-y. PMID: 38951460
Bhattad S, Rawat A, Gupta A, Suri D, Garg R, de Boer M, Kuijpers TW, Singh S
J Clin Immunol 2015 Nov;35(8):777-85. Epub 2015 Nov 13 doi: 10.1007/s10875-015-0212-y. PMID: 26563161
Nagaraja V, Stewart TE, Mackay SG, Glenn DW, Wakefield D, Boutlis CS
Laryngoscope 2015 Apr;125(4):852-5. Epub 2014 Aug 14 doi: 10.1002/lary.24874. PMID: 25124395
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Clinical prediction guides

Meuleman MS, Duval A, Grunenwald A, Rezola Artero M, Dermani M, Peliconi J, Revel M, Vieira-Martins P, Courbebaisse M, Parfait B, Lebeaux D, Friedlander G, Roumenina L, Chauvet S, Frémeaux-Bacchi V, Dragon-Durey MA
Clin Chim Acta 2024 Feb 1;554:117750. Epub 2024 Jan 2 doi: 10.1016/j.cca.2023.117750. PMID: 38176523
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Recent systematic reviews

Oprea Y, Antohi DR, Vague M, Delbourgo Patton C, Wu B, Ortega-Loayza AG
Am J Clin Dermatol 2024 Sep;25(5):701-716. Epub 2024 Jul 1 doi: 10.1007/s40257-024-00875-y. PMID: 38951460

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