Etiology, pathology and pathogenesis of acute necrotizing encephalopathy and acute encephalopathy with biphasic seizures and late reduced diffusion

为了阐明急性坏死性脑病(ANE)和伴有双相发作和迟发性弥散减少(AESD)的急性脑病的病因，进行了遗传学分析。我们通过一项全国性的合作研究收集了血液样本，并检测了候选基因的突变和多态。我们发现线粒体酶CPT2和腺苷受体ADORA2A的多态性使儿童易患AESD，某些人类白细胞抗原类型是ANE的危险因素。这些发现有助于确定这些综合征发病机制的关键分子。我们还发现，与高加索人的家族性ANE不同，日本散发性ANE与RANBP2突变无关。

To elucidate the etiology of acute necrotizing encephalopathy (ANE) and acute encephalopathy with biphasic seizures and late reduced diffusion (AESD),genetic analyses were performed. We collected blood samples by a nationwide collaborative study, and examined mutations and polymorphisms of candidate genes. We found that polymorphism of a mitochondrial enzyme, CPT2, and an adenosine receptor, ADORA2A,predisposes children to AESD, and that certain HLA types are a risk factor for ANE. These findings led to identification of key molecules of the pathomechanism of these syndromes.We also found that Japanese sporadic ANE is unrelated to mutation of RANBP2, unlike familial ANE in Caucasians.