Complement Component 8 Deficiency, Type 1 D84.1

Rare autosomal recessive immunodeficiency due to mutations in the C8A gene (120950) located on chromosome 1p32.2.

Patients with a deficiency of C8 suffer from recurrent neurological infections, especially meningococcal infections with rare serotypes (Kaufmann T et al 1993). A few isolated cases have identified SLE patients with C8 deficiency (Pickering RJ et al 1982).

In humans, two types of inherited C8 deficiency are known:

• Type I, in which only C8 alpha and C8 gamma are absent.
• Type II (613789), in which only C8 beta (C8B; 120960) is absent (Tedesco et al. 1983). Clinically, the two types are indistinguishable (Ross et al. 1984). (613790)

By screening for complement deficiency in 145,640 blood donors from Osaka and 92,686 donors from all of Japan, Fukumori et al. (1998) identified

• 5 individuals with C5 deficiency (609536) (2/100,000).
• 6 individuals with C6 deficiency (612446)
• 17 individuals with C7 deficiency (610102)
• 5 persons with C8 alpha/gamma deficiency (2/100,000)
• 439 individuals with C9 deficiency (613825).

Kojima et al (1998) identified three unrelated individuals with C8-alpha/gamma deficiency three C8A mutations in this collective, including the splice junction mutation at the boundary between exon 2 and intron 2 (120950.0002) and the nonsense mutation in exon 9 (120950.0003).

1. Fukumori Y et al.(1998) Terminal complement component deficiencies in Japan. Exp. Clin. Immunogenet 15: 244-248.
2. Kaufmann T et al (1993) Genetic basis of human complement C8 beta deficiency. J Immunol 150:4943-4947.
3. Kojima T et al (1998) Genetic basis of human complement C8 alpha-gamma deficiency. J Immun 161: 3762-3766.
4. Pickering RJ et al (1982) Identification of the alpha-gamma subunit of the eighth component of complement (C8) in a patient with systemic lupus erythematosus and absent C8 activity: patient and family studies. Clin Immunopath 23: 323-334.
5. Ross SC et al (1984) Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficient. Medicine 63: 243-273.
6. Tedesco F et al (1983) Two types of dysfunctional eighth component of complement (C8) molecules in C8 deficiency in man: reconstitution of normal C8 from the mixture of two abnormal C8 molecules. J Clin Invest 71: 183-191.
7. Tedesco F et al (1990) Two distinct abnormalities in patients with C8-alpha-gamma deficiency: low level of C8-beta chain and presence of dysfunctional C8-alpha-gamma subunit. J Clin Invest 86: 884-888.