Early complement pathway deficiencies predispose to invasive infections with encapsulated bacteria. C2 deficiency is the most common human complement deficiency, yet it may remain clinically silent until a life-threatening presentation. We describe a previously healthy 22-month-old male with fulminant pneumococcal meningitis and sepsis, diagnosed with C2 deficiency at the perimortem phase, with subsequent genetic confirmation in two asymptomatic siblings.
A previously healthy, fully immunized 22-month-old male presented with 2 days of fever and irritability followed by rapid deterioration, lethargy, and tachycardia. Cerebrospinal fluid (CSF) demonstrated pleocytosis with gram-positive cocci, and pneumococcal PCR was positive. Despite broad-spectrum meningitic-dose antimicrobials, fluid resuscitation, and pediatric intensive care unit (PICU) management including seizure control and mechanical ventilation, he developed multiorgan failure, severe cerebral edema, and radiologic evidence of compromised cerebral perfusion. Brain death was confirmed within 48 hours of PICU admission. Complement evaluation at the perimortem phase revealed markedly decreased classical pathway activity, with preserved alternative pathway function, consistent with a deficiency in the classical component. Targeted complement gene testing identified C2 deficiency. Genetic testing of two clinically well siblings showed the same C2 deficiency; both remain asymptomatic to date.
C2 deficiency may remain unrecognized until a sentinel, severe infection occurs. Children commonly present with invasive pneumococcal disease due to impaired opsonization of encapsulated organisms. While C2 deficiency is often associated with autoimmune features later in childhood, overwhelming infection remains the initial manifestation in a subset of cases. A fatal presentation in an otherwise healthy toddler highlights the importance of early complement testing in severe meningitis and the utility of family cascade screening.
Our patient emphasizes the importance of early recognition of complement deficiency in patients with fulminant pneumococcal meningitis despite vaccination and healthy preinfection status. Family screening enables anticipatory guidance, vaccination strategies, and prophylaxis considerations for relatives at risk.
