Adolescent onset of susceptibility to acute infection-induced encephalopathy-9 mimicking immune-mediated encephalitis

An early adolescent boy, born to a consanguineously married couple, with mild baseline developmental delay, presented with fever-triggered acute encephalopathy manifesting as ataxia, tremors and seizures. Neuroimaging revealed multifocal, symmetric involvement of the insular cortex, basal ganglia, temporo-occipital regions and cerebellum with diffusion restriction. Extensive infectious, autoimmune and metabolic evaluation during the first episode was inconclusive, and he was treated as immune-mediated encephalitis with partial recovery. Three months later, febrile illness precipitated a severe relapse with neurological regression, movement disorder and progressive cerebellar atrophy on follow-up imaging. Given the relapsing fever-triggered course, baseline developmental delay, incomplete recovery, negative autoimmune workup and progressive neuroimaging changes without new inflammatory lesions, a genetic aetiology was suspected. Genetic testing identified a homozygous variant in the NUP214 gene, supporting a diagnosis of acute infection-induced encephalopathy type 9. This case highlights the importance of considering genetic susceptibility in children with recurrent infection-triggered encephalopathy and atypical recovery.