Complement deficiency
Complement deficiency comprises inherited deficiencies of complement proteins whose clinical pattern predicts the risk: early classical-pathway (C1-C4) deficiency causes lupus-like autoimmunity and pyogenic infection, while terminal pathway (C5-C9) deficiency causes recurrent Neisseria infection. Diagnosis uses CH50 and AH50 screening with individual component levels, and prevention centers on meningococcal vaccination and antibacterial prophylaxis.
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What this article covers
- Overview
Definition: complement deficiency is a group of inherited deficiencies of individual complement proteins, whose position in the cascade predicts the clinical consequence.
- Epidemiology
Individually rare: C2 deficiency is the most common classical-pathway deficiency in populations of European descent.
- Risk factors
Inherited complement gene mutation: the underlying cause, mostly autosomal recessive.
- Pathophysiology
Classical pathway (C1-C4): needed to clear immune complexes and apoptotic cells and to opsonize encapsulated bacteria; deficiency causes immune-complex (lupus-like) disease and pyogenic infection.
- Clinical features
Recurrent Neisseria infection: meningococcemia or meningitis and disseminated gonococcal infection in terminal deficiency, often with milder or recurrent episodes.
- Differential diagnosis
Hereditary angioedema (C1-inhibitor deficiency): recurrent bradykinin-mediated angioedema, not infection.
- Diagnosis
Establish with complement functional screening followed by component levels: the diagnostic basis is a low total hemolytic complement (CH50, which screens the classical and terminal pathways) or low…
- Management
First, treat the acute infection: empiric ceftriaxone 2 g IV every 24 hours for suspected meningococcal disease, adjusted by site and cultures.
- Complications
Fulminant meningococcal disease: meningitis and meningococcemia, the principal life threat in terminal deficiency.
- Prognosis
Good with vaccination and prophylaxis: the risk of recurrent Neisseria disease falls substantially once preventive measures are in place.
- Prevention
Meningococcal vaccination (ACWY and B) with boosters is the central preventive measure, extended to pneumococcal and Hib vaccination.
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