Recurrent acute necrotizing encephalopathy following influenza A in a genetically predisposed family

Acute necrotizing encephalopathy (ANE) typically affects young, healthy children who develop rapid-onset severe encephalopathy triggered by viral infections. This disease is more commonly reported in Japan but occurs worldwide, although it remains under-recognized in Western countries. An autosomal dominant form, ANE1, was recently identified. We report the details of a 9-year-old Caucasian female who experienced recurrent ANE episodes at the ages of 9 months and 9 years. Brain magnetic resonance imaging findings were characteristic of ANE during both episodes, although more extensive in the recent episode, which resulted in severe neurological sequelae; influenza A was identified on bronchoalveolar lavage during this episode. Interestingly, there was evidence of peripheral polyneuropathy during the recent episode, which has not previously been described in sporadic ANE. Both the patient and her mother, who had also had postviral polyneuritis in the past, harbour a mutation in Ran-binding protein 2 (RANBP2); this occurred de novo in the mother and confers genetic susceptibility to ANE. Our case suggests that recurrent disease and/or an expanded clinical phenotype raises the possibility of ANE1; positive family history, although supportive, is not necessary as the mutation can occur de novo. Increased awareness may lead to earlier recognition and better treatment options.