title: Variable clinical course in acute necrotizing encephalopathy and identification of a novel RANBP2 mutation.
abstract: Acute necrotizing encephalopathy (ANE) is a rare disease presenting with rapidly progressing encephalopathy. It usually occurs in otherwise healthy children after common viral infections. The hallmarks of ANE are the neuroradiological findings of multiple symmetric lesions in the thalami, midbrain, pons and brainstem. Most cases are sporadic and non recurrent. However, recurrent or familial forms of ANE due to mutations in RANBP2 gene have been reported. It has been suggested to give these cases the term ANE1. We report the clinical course in two male infants (P1, P2) with ANE1 and a variable clinical course and outcome. One patient is heterozygous for the most common RANBP2 missense mutation p.Thr585Met. In the other patient we observed a novel de novo missense mutation p.Trp681Cys in the RANBP2 gene causing recurrent ANE. Clinical and radiological features are presented and differential diagnoses are discussed. This report adds to the current knowledge of the phenotype in ANE, caused by mutations in RANBP2 gene.
authors.affiliation: Klinik für Kinder- und Jugendmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany. Electronic address: Katharina.Sell@uniklinikum-dresden.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Sell
authors.affiliation: Abteilung Neuropädiatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Storch
authors.affiliation: Institut und Poliklinik für Radiologische Diagnostik, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hahn
authors.affiliation: Klinische Forschung, Klinik und Poliklinik für Kinder- und Jugendmedizin, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Min Ae
authors.initials: MA
authors.lastname: Lee-Kirsch
authors.affiliation: Child Neurology, Epilepsy, University Children's Hospital Zurich, Zurich, Switzerland.
authors.forename: Georgia
authors.initials: G
authors.lastname: Ramantani
authors.affiliation: Klinik für Neurologie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Jackson
authors.affiliation: Cincinnati Children's Hospital, Medical Center, OH, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Neilson
authors.affiliation: Abteilung Neuropädiatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Maja
authors.initials: M
authors.lastname: von der Hagen
authors.affiliation: Zentrum für Humangenetik und Institut für Humangenetik der Universität Regensburg, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Hehr
authors.affiliation: Abteilung Neuropädiatrie, Medizinische Fakultät Carl Gustav Carus, Technische Universität Dresden, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Smitka
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging; D003937:Diagnosis, Differential; D006801:Humans; D007223:Infant; D004684:Leukoencephalitis, Acute Hemorrhagic / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics*; D020125:Mutation, Missense; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D010641:Phenotype
chemical_list: D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; C094493:ran-binding protein 2
keywords: ANE; ANE1; Acute necrotizing encephalopathy; Encephalopathy; IIAE3; RANBP2