A 3-year-old girl presented to us in November 1998 with fever, headache and altered sensorium of two days duration. She was sick, irritable, drowsy and had neck rigidity. Blood counts showed leucocytosis. CSF came under high pressure and was turbid. It had 550 cells per mm3 with 65% poly-morphs and 35% lymphocytes. CSF proteins were 2 g/dL and glucose was 0.7 mg/dL. Gram stain showed gram positive cocci and CSF culture grew Streptococcus pneumoniae. She was treated with IV Ceftriaxone and made a complete and uneventful recovery. She presented again after 3½ with another episode of fever, lethargy and vomiting. CSF and blood culture again revealed streptococcus pneumoniae. She was again treated with IV Ceftriaxone and made complete recovery. She had a past history of two episodes of otitis media and one episode of Escherichia coli urinary tract infection.

In March 2002, her sibling, a boy aged 10 months presented with a short history of fever, vomiting and convulsions. Clinical diagnosis of acute meningitis was entertained. CSF and blood culture grew Streptococcus pneumoniae. He was also treated with IV Ceftriaxone and he made an uneventful recovery. He had chronic suppurative otitis media since the age of six months and also had recurrent chest infection and wheeze.

Family history showed three deaths due to probable meningitis (an uncle aged 28 years, a cousin aged nine years and sibling aged nine months).

In view of the history of recurrent infection and pneumococcal meningitis we investigated the two siblings for immunodeficiency. Both siblings had normal blood counts, immuno globulin levels and lymphocyte subsets. Total hemolytic complement activity, i.e., CH 50 was 28.5%in the first child and 33.7% in the second (Normal range: 80-100%). Complement C3 levels were 0.06 g/L in both which were very low (Normal range 0.7 to 1.6 g/L). Other complement levels were within normal limits. Complement levels in parents were within normal limits. A diagnosis of familial C3 complement deficiency was made.

Both patients were put on prophylactic antibiotics and were immunized with Pneumococcal and H. influenzae vaccines.

Complement deficiencies can present at any age and make children more prone to infections with capsulated organisms leading to meningitis or sepsis.

Deficiency of Classical pathway defect (C1, C4 and C2) can predispose to auto-immune diseases like systemic lupus erythematosus, rheumatoid arthritis, and glomerulonephritis. They also predispose to infections with capsulated organisms, i.e., Pneumococci and H.influenzae.

C3 deficiency can predispose to recurrent upper respiratory tract infections and also infections with capsulated organisms. Deficiencies of C5 to C9 i.e., membrane complex defect predisposes to infections with Neisseria. Defects in the alternative pathway of complement activation again predisposes to infections with capsulated organisms.

There is no curative treatment for complement deficiency. Prompt treatment of infections, prophylactic antibiotics and vaccination against pneumococci, H. influenzae and Meningococci forms the main stay of preventive treatment. Gene therapy is of promise in the near future.

Lt. Col. Dr. F.K. Otoo (Consultant Pediatrician) had a lead role in the diagnosis and management of these children.