Ohashi Eri, Hayakawa Itaru, Murofushi Yuka, Kawai Michiko, Suzuki-Muromoto Sato, Abe Yuichi, Yoshida Michiko, Kono Naoko, Kosaki Rika, Hoshino Ai, Mizuguchi Masashi, Kubota Masaya
Division of Neurology, National Center for Child Health and Development, Tokyo, Japan.
Division of Neurology, National Center for Child Health and Development, Tokyo, Japan.
Brain Dev. 2021 Sep;43(8):873-878. doi: 10.1016/j.braindev.2021.04.009. Epub 2021 May 28.
Acute necrotizing encephalopathy (ANE) is a severe encephalopathy associated with acute viral infection. While most ANE cases are sporadic, pathogenic variants in the gene RAN binding protein 2 (RANBP2) have been identified as a major cause of familial or recurrent ANE (ANE1). Although sporadic ANE predominantly affects Asian children, ANE1 is very rare in east Asia.
A 1-year-7-month-old boy, born to unrelated Japanese parents, presented with a seizure and impaired consciousness after 3 days of fever. Brain magnetic resonance imaging (MRI) showed a characteristic involvement of the bilateral thalami, external capsules, insular cortices, and brainstem, suggesting ANE. He received intravenous steroids. Two months later, he had another episode of acute encephalopathy during respiratory syncytial virus infection, from which he recovered relatively well. The recurrent encephalopathic episodes and the characteristic MRI suggested ANE1. Genetic analyses revealed two variants: a rare heterozygous missense variant of RANBP2 [c.1754C>T; p.Thr585Met], and a thermolabile polymorphism in carnitine palmitoyltransferase 2 (CPT2) [c. 1055T>G; p.Phe352Cys].
This is the first case of recurrent ANE with an RANBP2 mutation in Japan. The patient also harbored a CPT2 polymorphism that is linked to acute encephalopathy in Japanese patients. Thus, he had a genetic background with two susceptibility variants for acute encephalopathy, RANBP2 (frequent in the Caucasians), and CPT2 (frequent in the Japanese). Further studies are needed to fully discover the genetic predisposition to familial or recurrent ANE in the Asian population.
急性坏死性脑病（ANE）是一种与急性病毒感染相关的严重脑病。虽然大多数ANE病例为散发性，但已确定RAN结合蛋白2（RANBP2）基因的致病变异是家族性或复发性ANE（ANE1）的主要原因。尽管散发性ANE主要影响亚洲儿童，但ANE1在东亚非常罕见。
一名1岁7个月大的男孩，其父母为非近亲结婚的日本人，在发热3天后出现癫痫发作和意识障碍。脑磁共振成像（MRI）显示双侧丘脑、外囊、岛叶皮质和脑干有特征性受累，提示为ANE。他接受了静脉注射类固醇治疗。两个月后，他在呼吸道合胞病毒感染期间再次出现急性脑病发作，恢复情况相对较好。反复出现的脑病发作和特征性MRI提示为ANE1。基因分析发现了两个变异：一个罕见的RANBP2杂合错义变异[c.1754C>T；p.Thr585Met]，以及肉碱棕榈酰转移酶2（CPT2）中的一个热不稳定多态性[c.1055T>G；p.Phe352Cys]。
这是日本首例伴有RANBP2突变的复发性ANE病例。该患者还存在一种与日本患者急性脑病相关的CPT2多态性。因此，他具有急性脑病的两种易感性变异的遗传背景，即RANBP2（在白种人中常见）和CPT2（在日本人中常见）。需要进一步研究以充分发现亚洲人群中家族性或复发性ANE的遗传易感性。
