# Disseminated gonococcal infection secondary to a rare homozygous mutation resulting in complement factor I deficiency

## TL;DR

A rare genetic mutation causing complement factor I deficiency led to a severe gonococcal infection in a patient with a history of vasculitis.

## Contribution

This case highlights the role of complement factor I deficiency in predisposing to disseminated gonococcal infection.

## Key findings

- A homozygous nonsense mutation in CFI was identified, leading to complete FI deficiency.
- Low complement activity and consumption were observed in the patient.
- The patient's serum contained IgG antibodies against gonococcal and meningococcal antigens.

## Abstract

We report a case of disseminated gonococcal infection linked to complement factor I (FI) deficiency, with a prior vasculitis-like episode. FI deficiency should be suspected in the setting of complement consumption, characterized by low levels of multiple complement components.

A 34-year-old male presented with recurrent fever, arthralgia, and rash. He had two prior hospitalizations for suspected vasculitis and meningococcal meningitis at age 13 years. Positive blood cultures for Neisseria gonorrhoeae established the diagnosis of disseminated gonococcal infection. Complement studies showed low total (CH50) and alternative pathway (AP50) activity and low levels of all alternative and terminal complement proteins and the complement inhibitors factor H and factor I (FI), suggesting uninhibited complement activation and complement consumption. A homozygous nonsense mutation leading to a premature stop codon (p.Arg474*, or R456X) in CFI predicted complete FI deficiency, which was confirmed by immunoblotting. The patient’s serum contained IgG against reduction-modifiable protein and the lipoproteins H.8 and lipidated azurin, which are targets for blocking antibodies against gonococci and meningococci, respectively. This report underscores the importance of considering FI deficiency in patients with invasive neisserial infections, vasculitis-like manifestations, and consumptive complementopathy.