South African patients with genetic deficiencies of complement components C5 and C6 suffer a marked increase in susceptibility to meningococcal disease : invited review

South African Black African and Cape Coloured patients who had suffered culture positive meningococcal disease (MD) were investigated for mutations in genes coding for the terminal complement pathway proteins C5 and C6. C5 mutations p.Q19X, p.R1476X and p.A252T are known to cause absent or very low serum C5levels and thus increased susceptibility of meningococcal disease. In addition for C6 deficiency genes are also responsible for increased susceptibility to the meningococcus and they too segregate in the Western Cape. We tested admission samples from the 81 black patients and 84 coloured patients for the three C5 mutations and four C6 mutations responsible for the deficiencies. Among the 81 black MD patients we found six C5 deficient p.A252T homozygous individuals and 17 C6 deficient individuals. Thus 28% of black patients who had suffered MD were complement deficient and vulnerable to further MD infections. We found no homozygous C5 deficient coloured MD patients, however 7 out of 84 (8%) coloured patients were C6 deficient. Thus the risk of recurrent MD infections is present for both groups but highest among black individuals. We strongly recommend antibiotic prophylaxis against further infections for terminal complement component deficient patients.