Familial acute necrotizing encephalopathy with RANBP2 mutation: The first report in Northeast Asia.
BACKGROUND
Acute necrotizing encephalopathy (ANE) is a rare but rapidly progressing encephalopathy following a febrile illness, commonly a viral infection. It is characterized by the features of acute encephalopathy such as seizure, alteration of consciousness, and symmetric involvement of the bilateral thalamus on neuroimaging tests. Although most ANE cases have occurred sporadically, familial or recurrent ANE has been reported in Caucasian patients, with genetic susceptibility to ANE noted in some patients due to a RANBP2 mutation. We report the cases of two Korean siblings with typical ANE and RANBP2 mutation.


METHODS
A 2year-old Korean girl presented with prolonged seizures and encephalopathy after two days of febrile illness. Brain computed tomography (CT) showed diffuse brain swelling and low attenuation in the bilateral thalamus. Two months later, her younger sister presented with lethargy and flurries of seizures after a Mycoplasma pneumoniae infection. Brain magnetic resonance imaging scan (MRI) showed a characteristic involvement of the bilateral thalamus, suggesting ANE. Although they received intravenous steroids and immunoglobulin, the older child died; her sister remained in a coma. Both were diagnosed with familial ANE after identifying a common missense mutation in RANBP2 (c.1754C>T: p.Thr585Met) in the younger sister and their father.


CONCLUSIONS
This report is the first case of familial ANE in Northeast Asia identifying a RANBP2 mutation with poor outcome. Due to rapidly deterioration and recurrent nature of familial ANE, genetic test of RANBP2 mutation should be considered for early diagnosis. Further studies are needed to elucidate the nature of ANE.
Department of Pediatrics, Kyungpook National University Children's Hospital, Daegu, South Korea.
Yun-Jeong
YJ
Lee
Department of Pediatrics, Kyungpook National University Children's Hospital, Daegu, South Korea.
Su-Kyeong
SK
Hwang
Department of Radiology, Kyungpook National University College of Medicine, Kyungpook National University Hospital, Daegu, South Korea.
So Mi
SM
Lee
Department of Pediatrics, Kyungpook National University Children's Hospital, Daegu, South Korea. Electronic address: shkwon@knu.ac.kr.
Soonhak
S
Kwon
D044466:Asian People / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging*; D002675:Child, Preschool; D003937:Diagnosis, Differential; D017809:Fatal Outcome; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007723:Korea; D004684:Leukoencephalitis, Acute Hemorrhagic / Q000000981:diagnostic imaging / Q000235:genetics* / Q000628:therapy; D018832:Molecular Chaperones / Q000235:genetics*; D009154:Mutation; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D035781:Siblings
D018832:Molecular Chaperones; D028861:Nuclear Pore Complex Proteins; C094493:ran-binding protein 2
Acute necrotizing encephalopathy; Familial; RANBP2