Complement Factor I Deficiency With Acute Hemorrhagic Leukoencephalitis and Longitudinally Extensive Transverse...

Area of Science:

• Neuroimmunology
• Complement System Biology
• Rare Genetic Disorders

Background:

• Complement factor I (CFI) deficiency is a rare genetic disorder.
• It can manifest as severe, relapsing central nervous system (CNS) autoinflammation.
• Unexplained neuroinflammation poses diagnostic challenges.

Purpose of the Study:

• To report a case of partial CFI deficiency presenting with fulminant CNS autoinflammation.
• To highlight the diagnostic utility of genetic testing in unexplained neuroinflammatory conditions.
• To evaluate the efficacy of IL-1 receptor antagonism in this context.

Main Methods:

• Case report of a young adult with acute hemorrhagic leukoencephalitis and transverse myelitis.
• In-hospital whole-genome sequencing and complement testing.
• Cerebrospinal fluid (CSF) profiling, including cytokine and gene expression analysis.
• Treatment with IL-1 receptor antagonist (anakinra).

Main Results:

• Partial CFI deficiency was diagnosed via genetic and complement testing.
• CSF analysis revealed neutrophil and pro-inflammatory cytokine elevation, with gene expression patterns suggesting innate immune hyperactivity.
• IL-1 receptor antagonism led to sustained suppression of autoinflammatory attacks.
• Neurologic recovery was observed.

Conclusions:

• CFI deficiency can present as fulminant, relapsing CNS autoinflammation, potentially triggered by infections.
• Genetic testing is crucial for diagnosing unexplained neuroinflammation.
• Targeted therapy with IL-1 receptor antagonists can be effective in managing this rare and severe condition, improving outcomes.