Complement factor I (CFI) is a serine protease that inactivates complement C3b and C4b in the presence of cofactors. Complete CFI deficiency leads to a secondary complement deficiency due to uncontrolled amplification of C3 cleavage leading to a severe C3 deficiency. CFI deficiency can lead to severe infections particularly with encapsulated organisms early in life in addition to atypical HUS and autoimmune diseases.
Here, we present a case of a previously healthy 13-month-old girl who developed pseudomonas septic arthritis and was found to have CFI deficiency. She first presented with acute onset right knee swelling and refusal to walk without any inciting trigger. Her only prior infection was one episode of acute otitis media. She underwent intraoperative irrigation and debridement of the knee and cultures subsequently grew Pseudomonas aeruginosa. She completed a course of antibiotics with cefepime followed by oral levofloxacin with clinical improvement. Immunologic laboratory evaluation revealed low CH50 on three samples 3 months apart (16.1, 31.1, and 16.4 U/mL) with low C3 (53 mg/dL) and normal C4. She also had unremarkable DHR, quantitative immunoglobulins, lymphocyte enumeration, mitogen response, vaccine titers after completing immunization series, red blood cell pitting, and TLR assay. Genetic testing was then performed that revealed a pathogenic homozygous mutation (c.80_81del, p.Asp27Alafs*18) consistent with a diagnosis of autosomal recessive CFI deficiency.
Management recommendations included hypervaccination with the conjugated pneumococcal vaccine and meningococcal (MenACWY and MenB) vaccines and consideration of prophylactic antibiotics. The clinical phenotype in CFI deficiency is driven by the CFI variant; some heterozygous variants lead to atypical HUS and age-related macular degeneration, while other homozygous variants are associated with neuroinflammation, glomerulonephritis, or autoimmunity. Our patient’s variant results in a premature translational stop signal and has been associated with infection and recurrent IgA vasculitis. Further understanding the risks associated with different variants may help guide patient care and screening. This case highlights the importance of noting and further evaluating a decreased but nonzero CH50 in a patient with a severe sentinel infection for complement pathway deficiencies in addition to using a personalized medicine approach for care and other disease manifestation screening.
