Pearls & Oy-sters: Homozygous Complement Factor I Deficiency Presenting as Fulminant Relapsing Complement-Mediated...

Area of Science:

• Immunology
• Neurology
• Genetics

Background:

• The complement system, particularly the alternative pathway, plays a crucial role in innate immunity.
• Complement factor I (CFI) is essential for regulating complement activation.
• Deficiency in CFI can lead to uncontrolled complement activity and systemic inflammation.

Observation:

• A 36-year-old male presented with recurrent neurological episodes including fever, headache, altered mental status, and focal deficits.
• Neuroimaging showed reversible white matter lesions, and laboratory tests revealed low C3, low factor B, and absent alternative pathway activity.
• A biopsy confirmed neutrophilic vasculitis.

Findings:

• Genetic analysis identified a homozygous pathogenic variant in the complement factor I (CFI) gene.
• This deficiency resulted in overactive alternative complement pathway, leading to consumption of C3 and factor B.
• The patient's condition stabilized upon initiation of IL-1β inhibition therapy.

Implications:

• Complement factor I deficiency is a rare but significant cause of relapsing neurological disease.
• This case underscores the importance of considering complement disorders in patients with unexplained neurological and inflammatory symptoms.
• Targeting IL-1β may represent a viable therapeutic strategy for complement-mediated neurological conditions.