Complement component 3 deficiency, autosomal recessiveD84.1

C3 deficiency (613779) is caused by a homozygous or compound heterozygous mutation in the C3 gene (120700) on chromosome 19p13

Pussell et al (1980) described a family in which three children had homozygous C3 deficiency and both parents and two other children were heterozygous for a C3 null gene. The parents were presumably cousins. The homozygous and heterozygous children were prone to infections. Proteinuria and/or microscopic hematuria were present in all 3 homozygous children, and one heterozygous child had membranoproliferative glomerulonephritis. The only child with normal complement had neither nephritis nor increased susceptibility to infection.

Sano et al (1981) reported 2 sisters with C3 deficiency and SLE-like symptoms.

Berger et al (1983) and Borzy et al (1988) observed C3-deficient homozygotes who developed mesangiocapillary glomerulonephritis. It was suggested that the association between C3 deficiency and nephritis was due to the failure of a second physiological activity of the complement system, namely, the promotion of immune complex disposal by the mononuclear phagocytic system.

Nilsson et al (1992) described three sisters with dysfunctional C3 allele. Complement function of the alternative pathway was absent, and complement function of the classical pathway was partially intact. One of the sisters, had SLE-like disease.

Botto et al (1990) described a 10-year-old boy with recurrent otitis media during the first three years of life. Between the ages of 5 and 8 years, he had approximately 20 episodes of erythema multiforme (face, forearms, and hands). The episodes were usually preceded by an upper respiratory tract infection, and a group A beta-hemolytic streptococcus was isolated from his throat during two episodes. C3 could not be detected in the patient's serum.

1. Berger M et al (1983) Circulating immune complexes and glomerulonephritis in a patient with congenital absence of the third component of complement. New Engl J Med 308: 1009-1012.
2. Botto M et al (1990) Molecular basis of polymorphisms of human complement component C3. J Exp Med 172: 1011-1017.
3. McLean et al (1980) Partial lipodystrophy and familial C3 deficiency. Hum. Hered. 30: 149-154.
4. McLean RH et al (1980) Familial partial deficiency of the third component of complement (C3) and the hypocomplementemic cutaneous vasculitis syndrome. Am J Med 68: 549-558.
5. Nilsson UR et al (1992) Hereditary dysfunction of the third component of complement associated with a systemic lupus erythematosus-like syndrome and meningococcal meningitis. Arthritis Rheum 35: 580-586.
6. Osofsky SG et al (1977) Hereditary deficiency of 3rd component of complement in a child with fever, skin rash, and arthralgias--response to transfusion of whole blood. J Pediat 90: 180-186.
7. Pussell BA et al (1980) Complement deficiency and nephritis: a report of a family. Lancet 315: 675-677.
8. Reis ES et al. (2006) Clinical aspects and molecular basis of primary deficiencies of complement component C3 and its regulatory proteins factor I and factor H. Scand. J. Immunol. 63: 155-168.
9. SanoY et al. (1981) Hereditary deficiency of the third component of complement in two sisters with systemic lupus erythematosus-like symptoms. Arthritis Rheum 24: 1255-1260.
10. Tsukamoto H et al. (2005) Molecular analysis of a novel hereditary C3 deficiency with systemic lupus erythematosus. Biochem Biophys Res Commun 330: 298-304.