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Type I complement component 8 deficiency(C8D1)

MedGen UID:: 462431
•Concept ID:: C3151081
•: Disease or Syndrome

Synonyms:	C8 alpha-gamma deficiency; C8 deficiency type I; C81 deficiency; C8AG DEFICIENCY; COMPLEMENT C8 DEFICIENCY, TYPE I; Complement component 8 deficiency type 1

Gene (location): Gene(s) directly associated with this condition or phenotype.	C8A (1p32.2)

Monarch Initiative:	MONDO:0013422
OMIM®:	613790

Definition

Patients with deficiency of C8 suffer from recurrent neisserial infections, predominantly with meningococcus infection of rare serotypes. Most such patients are discovered among those having their first episode of meningitis at ages older than 10 years (Ross and Densen, 1984). Two kinds of inherited C8 deficiency have been reported in humans: type I (C8D1), in which only C8 alpha and C8 gamma (C8G; 120930) are deficient, and type II (C8D2; 613789), in which only C8 beta (C8B; 120960) is deficient (Marcus et al., 1982; Tedesco et al., 1983). The 2 types are clinically indistinguishable (Ross and Densen, 1984). [from OMIM]

Additional description

From MedlinePlus Genetics
The severity of complement component 8 deficiency varies widely. While some people with this condition experience one or more infections, others do not have any health problems related to the disorder.

There are two types of complement component 8 deficiency, types I and II, classified by their genetic cause. The two types have the same signs and symptoms.

Complement component 8 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. People with complement component 8 deficiency have a significantly increased risk of recurrent bacterial infections, particularly by a bacterium called Neisseria meningitidis. Infection by this bacterium causes inflammation of the membranes surrounding the brain and spinal cord (meningitis). Although meningitis can be life-threatening, individuals with complement component 8 deficiency are less likely to die from the infection than people in the general population who contract it. https://medlineplus.gov/genetics/condition/complement-component-8-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.

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Meningitis

MedGen UID:: 6298
•Concept ID:: C0025289
•: Disease or Syndrome

Inflammation of the meninges.

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Decreased circulating complement C8 concentration

MedGen UID:: 462432
•Concept ID:: C3151082
•: Finding

Concentration of the complement component C8 in the blood circulation below the lower limit of normal.

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Abnormality of the immune system

Recent clinical studies

Etiology

Inherited Classical and Alternative Pathway Complement Deficiencies in Children: A Single Center Experience.

Genel F, Erdem SB, Gülez N, Karaman S, Nacaroglu HT, Skattum L, Truedsson L
Iran J Immunol 2018 Dec;15(4):309-320. doi: 10.22034/IJI.2018.39400. PMID: 30593745

Complement deficiency and antibody profile in survivors of meningococcal meningitis due to common serogroups in Italy.

D'Amelio R, Agostoni A, Biselli R, Brai M, Caruso G, Cicardi M, Corvetta A, Fontana L, Misiano G, Perricone R
Scand J Immunol 1992 May;35(5):589-95. doi: 10.1111/j.1365-3083.1992.tb03258.x. PMID: 1579859

Genetic aspects of complement component C8 in Norwegian meningococcal disease patients.

Rogde S, Høiby EA, Teisberg P, Olaisen B
Scand J Infect Dis 1990;22(6):673-9. doi: 10.3109/00365549009027120. PMID: 2284574

Prevalence of congenital or acquired complement deficiency in patients with sporadic meningococcal disease.

Ellison RT 3rd, Kohler PF, Curd JG, Judson FN, Reller LB
N Engl J Med 1983 Apr 21;308(16):913-6. doi: 10.1056/NEJM198304213081601. PMID: 6835295

See all (4)

Diagnosis

Inherited Classical and Alternative Pathway Complement Deficiencies in Children: A Single Center Experience.

Genel F, Erdem SB, Gülez N, Karaman S, Nacaroglu HT, Skattum L, Truedsson L
Iran J Immunol 2018 Dec;15(4):309-320. doi: 10.22034/IJI.2018.39400. PMID: 30593745

Fluid phase generation of terminal complement complex as a novel index of bioincompatibility.

Deppisch R, Schmitt V, Bommer J, Hänsch GM, Ritz E, Rauterberg EW
Kidney Int 1990 Feb;37(2):696-706. doi: 10.1038/ki.1990.36. PMID: 2407885

Influence of subinhibitory concentrations of cephalosporins on the serum sensitivity of Pseudomonas aeruginosa.

Darveau RP, Cunningham MD
J Infect Dis 1990 Oct;162(4):914-21. doi: 10.1093/infdis/162.4.914. PMID: 2119402

Enhanced reactive lysis of paroxysmal nocturnal hemoglobinuria erythrocytes by C5b-9 does not involve increased C7 binding or cell-bound C3b.

Rosenfeld SI, Jenkins DE Jr, Leddy JP
J Immunol 1985 Jan;134(1):506-11. PMID: 3964820

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Therapy

Fluid phase generation of terminal complement complex as a novel index of bioincompatibility.

Deppisch R, Schmitt V, Bommer J, Hänsch GM, Ritz E, Rauterberg EW
Kidney Int 1990 Feb;37(2):696-706. doi: 10.1038/ki.1990.36. PMID: 2407885

See all (1)

Prognosis

Inherited Classical and Alternative Pathway Complement Deficiencies in Children: A Single Center Experience.

Genel F, Erdem SB, Gülez N, Karaman S, Nacaroglu HT, Skattum L, Truedsson L
Iran J Immunol 2018 Dec;15(4):309-320. doi: 10.22034/IJI.2018.39400. PMID: 30593745

See all (1)

Clinical prediction guides

A Point Mutation Creating a 3' Splice Site in C8A Is a Predominant Cause of C8α-γ Deficiency in African Americans.

Densen P, Ackermann L, Saucedo L, Figueroa JE, Si ZH, Stoltzfus CM
J Immunol 2020 Sep 15;205(6):1535-1539. Epub 2020 Aug 7 doi: 10.4049/jimmunol.2000272. PMID: 32769119 Free PMC Article

Induced expression of neuronal membrane attack complex and cell death by Alzheimer's beta-amyloid peptide.

Shen Y, Sullivan T, Lee CM, Meri S, Shiosaki K, Lin CW
Brain Res 1998 Jun 15;796(1-2):187-97. doi: 10.1016/s0006-8993(98)00346-1. PMID: 9689469

Influence of subinhibitory concentrations of cephalosporins on the serum sensitivity of Pseudomonas aeruginosa.

Darveau RP, Cunningham MD
J Infect Dis 1990 Oct;162(4):914-21. doi: 10.1093/infdis/162.4.914. PMID: 2119402

Anti-idiotypic antibodies derived against C8, C9 and perforin bind homologous restriction factor.

Young JD, Jiang S, Liu CC, Hasselkus-Light CS
J Immunol Methods 1990 Mar 27;128(1):133-42. doi: 10.1016/0022-1759(90)90472-8. PMID: 1691232

Isolation and characterization of a membrane protein from normal human erythrocytes that inhibits reactive lysis of the erythrocytes of paroxysmal nocturnal hemoglobinuria.

Holguin MH, Fredrick LR, Bernshaw NJ, Wilcox LA, Parker CJ
J Clin Invest 1989 Jul;84(1):7-17. doi: 10.1172/JCI114172. PMID: 2738160 Free PMC Article

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