C4a-Defizienz-Syndrom, autosomal rezessives D84.1

Rare deficiency of the complement component C4a induced by mutations in the C4A gene. This protein is a non-enzymatic component of C3 and C5 convertases and thus essential for the propagation of the classical complement pathway.C4a protein deficiency is associated with systemic lupus erythematosus and type I diabetes mellitus.

In a screening of 42,000 healthy Japanese, partial C4 deficiency was found in 3 individuals (Torisu et al. 1970).

East Asian patients with low serum complement levels were found to have a high frequency of anti-double-stranded DNA antibodies, hemolytic anemia, and renal disease. Most East Asian subjects with C4A deficiency (unlike Europeans) were found to have a recombinant haplotype with bimodular C4 long and short genes encoding C4B1 and C4B96 (Chen JYet al. 2016).

Vergani et al (1985) demonstrated low serum C4 levels in 18 (69%) and low serum C3 levels in 5 (19%) of 26 patients with autoimmune chronic active hepatitis that began in childhood. The associated features indicated a defect in C4 synthesis.

Other authors demonstrated associations between homozygous deficiency of C4A and systemic lupus erythematosus (152700) or type I diabetes mellitus. Homozygous deficiency of C4B has been associated with susceptibility to bacterial meningitis (Winkelstein, 1987).

Lhotta et al (1990) described a patient with complete deficiency and renal disease who developed severe Schönlein-Henoch purpura with renal involvement at the age of 17. Six years later, he developed hypertension and a nephrotic syndrome that required hemodialysis followed by renal transplantation.

1. Chen JYet al. (2016) Effects of Complement C4 Gene Copy Number Variations, Size Dichotomy, and C4A Deficiency on Genetic Risk and Clinical Presentation of Systemic Lupus Erythematosus in East Asian Populations. Arthritis Rheumatol 68:1442-1453.
2. Lhotta K et al (1990) Renal disease in a patient with hereditary complete deficiency of the fourth component of complement. Nephron 56: 206-211.
3. Torisu, M et al (1970) Deficiency of the fourth component of complement in man. J Immunogenet 104: 728-737.
4. Vergani D et al (1985) Genetically determined low C4: a predisposing factor to autoimmune chronic active hepatitis. Lancet 325: 294-298.