Recurrent acute hemorrhagic necrotizing encephalopathy associated with RAN-binding protein-2 gene mutation in a pediatric patient

Abstract

A young male child presented with recurrent episodes of seizures and altered mental status following febrile episodes on three separate occasions between his first and third birthdays. Laboratory evaluations identified SARS-CoV-2 infection during the first episode and no infective agents or antibodies in the CSF during all the episodes. Brain imaging with CT and MRI revealed bilaterally symmetric patchy hemorrhagic necrotic foci in the deep brain nuclei and medial temporal lobes, prompting suspicion for an underlying predisposition to recurrent acute hemorrhagic necrotizing encephalopathy (rAHNE). Gene analysis confirmed a mutation in the RAN-Binding Protein-2 (RANBP2) gene. The patient made good recovery following treatment with IVIG, steroids and plasmapheresis, and follow-up brain imaging showed no progression of brain lesions. Early suspicion from characteristic imaging features in appropriate clinical settings will inform timely appropriate treatment and better outcome. We therefore provided short review of imaging features of AHNE.

Recurrent infection triggered encephalopathy syndrome in a pediatric patient with RANBP2 mutation and severe acute respiratory syndrome coronavirus 2 infection

“…19 To date, five patients with ANE associated with the 2019 coronavirus disease (COVID- 19) have been reported to carry the RANBP2 gene mutation. 3,4,6,9 Here we report a case of recurrent ITES in a pediatric patient with RANBP2 gene mutation who was diagnosed with influenza-associated encephalopathy and COVID-19-related ANE successively.…”

“…necrotizing encephalopathy (ANE), the most severe and fatal subtype of infection-triggered encephalopathy syndrome (ITES), in both children and adults. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] Studies have found that RANBP2 missense mutations predispose individuals to ANE. Neilson et al 18 reported familial, recurrent ANE (also termed ANE1) cases for the first time and confirmed that missense mutations in the RANBP2 gene are responsible for the genetic susceptibility to ANE.…”

“…Since the end of 2019, the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has gradually become prevalent worldwide. SARS‐CoV‐2 can cause acute necrotizing encephalopathy (ANE), the most severe and fatal subtype of infection‐triggered encephalopathy syndrome (ITES), in both children and adults 1–17 . Studies have found that RANBP2 missense mutations predispose individuals to ANE.…”

Intense work-up is required for pediatric COVID-related acute necrotizing encephalopathy with RANBP2 variants

“…A limitation of the study is that differentials of ANE were not appropriately ruled out. RANBP2 variants can be also associated with acute, hemorrhagic, necrotizing leucoencephalopathy (AHNE) [ 2 ]. Therefore, we should know if there were any indications for bleeding.…”

Letter to the Editor in response to Dr. Josef Finsterer et al. “Intense work-up is required for pediatric COVID-related acute necrotizing encephalopathy with RANBP2 variants”

“…A recent manuscript published after we submitted our paper reported a single case of acute necrotizing encephalopathy associated to Covid-19 with RANBP2 pathogenic variants in whom micro hemorrhagic foci were also detected by SWI sequences on MRI. The authors called it AHNE but we argue the appropriateness of this term since there were only microhemorrhages and the patient was carrier of RANBP2 pathogenic variant confirming the diagnosis of ANE1 [ 3 ].…”