Meningococcal meningitis in familial deficiency of the fifth component of complement

Absence of the fifth component of complement (C5) by immunochemical assay and marked deficiency by hemolytic assay (less than 0.1%) was found in a family in which the oldest male child had suffered severe and recurrent meningococcemia at age 15 years, two brothers developed meningococcal meningitis four years later (at ages 18 and 14 years), and a sister had the gonococcal arthritis-dermatitis syndrome. Although group-specific meningococcal antibody was present in the sera from all four siblings, serum bactericidal activity against Neisseria meningitidis could be demonstrated only in the presence of exogenous rabbit complement. Serum total hemolytic complement activity was undetectable in all four, but was restored to normal by the addition of purified C5. Subsequently, a second episode of group Y meningococcal meningitis was experienced by one brother and presumed gonococcal arthritis-dermatitis syndrome recurred in the sister. The family is the largest C5-deficient kindred to be reported and emphasizes the importance of C5 in host susceptibility to invasive Neisseria infections. In contrast to the peak incidence of N meningitidis disease in the general population in the first year of life, age of onset of meningococcal infection in these patients and in the 13 previously reported patients with terminal complement component deficiency has usually been in adolescence and early adulthood.