Thermolabile CPT II variants and low blood ATP levels are closely related to severity of acute encephalopathy in Japanese children
Thermolabile CPT II variants and low blood ATP levels are closely related to severity of acute encephalopathy in Japanese children
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DOI：
10.1016/j.braindev.2010.12.012
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发表时间：
2012-01-01
影响因子：
1.7
通讯作者：
Kido, Hiroshi
中科院分区：
文献类型：
--
作者：
Kubota, Masaya;Chida, Junji;Kido, Hiroshi
尽管停药后Reye综合征发生率下降，但急性脑病（非Reye综合征型）在日本仍不断报道。最近的研究表明，肉碱棕榈酰基转移酶II （CPT II）变异[F352C]的耐热表型与日本人流感相关脑病（IAE）的发病机制密切相关，在高热时引起线粒体ATP利用失败，导致脑水肿。因此，我们分别分析了12例和10例急性脑病患者的CPT II多态性和外周血ATP水平作为“能量危机”的信号。在12例急性脑病患者中，6例出现耐热性CPT II变异[F352C]，其中2例患者在重症监护下死亡。相比之下，其余6例无耐热性CPT II变异体[F352C]的患者表现出相对温和的临床病程。10例脑病急性期患者血ATP水平明显低于恢复期及热性惊厥状态患者。我们的数据表明，仅在日本发现的耐热性F352C CPT II变异可能是触发日本人群急性脑病病理机制的易感因素之一，并且与疾病的严重程度有因果关系。血液ATP水平的下降似乎反映了脑病急性期包括血脑屏障在内的全身性线粒体功能障碍。(C) 2011日本儿童神经病学学会。Elsevier B.V.版权所有。
Despite the decrease in Reye syndrome after the discontinuation of aspirin, acute encephalopathy (non-Reye syndrome type) has been continually reported in Japan. Recent studies suggested that the thermolabile phenotype of carnitine palmitoyltransferase II (CPT II) variation [F352C] was closely related to the pathomechanism of influenza-associated encephalopathy (IAE) in Japanese, causing mitochondrial ATP utilization failure during periods of high fever, resulting in brain edema. So, we analyzed CPT II polymorphism and peripheral blood ATP levels as a signal of "energy crisis" in 12 and 10 patients with acute encephalopathy, respectively. Out of the 12 patients with acute encephalopathy, six showed thermolabile CPT II variants [F352C], and of these six, two patients died in spite of intensive care. In contrast, the remaining six patients with no thermolabile CPT II variant [F352C] showed a relatively mild clinical course. Blood ATP levels of the 10 patients in the acute phase of encephalopathy were significantly lower than those during the convalescent phase and also those of patients with febrile seizure status. Our data suggest that the thermolabile F352C CPT II variant, found only in Japanese, might be one of the predisposing factors to trigger the pathomechanism of acute encephalopathy in the Japanese population, and that it is causally related to the severity of disease. The decreased blood ATP level seems to reflect systemic mitochondrial dysfunction including the blood brain barrier during the acute phase of encephalopathy. (C) 2011 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.