Poster Presentations

We present a 10-year-old boy with FIRES following gastrointestinal illness and genetic diagnosis of Complement Factor I deficiency. This is a rare but potentially treatable condition and should be considered in FIRES. He had super refractory status epilepticus with a clinical course and EEG supporting FIRES. He was unresponsive to antiepileptics, anaesthetics and immunosuppression. Extensive infectious, toxic, metabolic and autoimmune testing were negative. His MRI brain demonstrated T2 signal changes in corpus striatum, claustra, insular cortices and basal ganglia. He had pneumococcal empyema and Henoch Schonlein purpura in the past. This, with decreased C3 and C4 suggested factor I deficiency. Extended testing demonstrated very low factor B (58 mg/L), extremely high C5-b9 >1750 ng/L with absent CH50 and AP50. Complement factor I was undetectable in serum (<7 mg/L). Rapid exome sequencing confirmed diagnosis with homozygous CFI mutation. Factor I deficiency produces consumptive deficiency of C3 with resultant immunodeficiency and susceptibility to infection. Although plasma infusion/exchange may have restored factor I levels this was not undertaken due to the hypothetical risk of rapid conversion of C3b to the pro-inflammatory iC3b upon delivery of the exogenous factor I. Eculizumab, a complement C5 inhibitor, was initially licenced to treat paroxysmal nocturnal haemoglobinuria and atypical haemolytic uraemic syndrome but recently used to treat severe neuroinflammatory disease. Due to refractory seizures and very high C5b-9 levels it was planned to block terminal complement pathway hoping it would improve clinical course. We were unable to do this due to candidemia and LRTI. Fortunately, his seizures settled after 8 weeks on combination of Perampanel, Carbamazepine, Clobazam and Ketogenic diet. He is making progress with neurorehabilitation, however, complement activation levels are high and we would use Eculizumab if he deteriorated. This case highlights importance of thorough past medical history, checking of C3 and C4 and early recognition may improve outcome.