Case Studies

 Case 3.6 Isolated deficiency of complement component

A 26-year-old West Indian man presented with a 24-h history of occipital headache and vomiting. He was pyrexial (temperature 38.3°C), confused, irritable and had marked neck stiffness with a positive Kernig's sign. There was no other history of serious infections. His immediate family were healthy.

Lumbar puncture produced turbid cerebrospinal fluid (CSF) with a protein concentration of 4.5g/l (NR 0.1-0.4), glucose content of less than 0.1mmol/l (NR 2.5-4.0) and a leucocyte count of 8000/mm³ (97% neutrophils). Neisseria meningitidis was cultured from the CSF. The patient was treated with intravenous penicillin and oral chloramphenicol and made a rapid recovery over the following 2 weeks.

A search was made for an underlying cause of his meningitis. X-rays of the skull and sinuses showed no abnormal communication with the CSF. The possibility of an underlying immune defect was then considered and the results of immunological tests are shown in Table C3.6. Antibody production to a variety of bacterial and viral antigens was normal. However, total classical pathway haemolytic complement activity (CH50) and alternate pathway (AP 50) were consistently undetectable in his serum during convalescence, indicating a complete functional absence of one or more complement components of the terminal lytic pathway. Eventually, he was shown to have an isolated deficiency of C6, with normal levels of all other components. Half normal levels of C6 were found in the sera of his parents and in three of his four siblings: the other had a normal level.

Unlike immunoglobulin deficiency, long-term replacement of missing complement components is not feasible at present because their half-lives are so short (<1 day). Nasopharyngeal carriage of N. meningitidis by the patient and his close contacts can be eradicated by antibiotics but at the risk of inducing resistant strains. Prophylactic penicillin is used in those patients with symptomatic complement deficiencies.

Table C3.6 Immunological investigations* in Case 3.6.

*Normal ranges (NR) shown in brackets.