POLG1 manifestations in childhood
POLG1 manifestations in childhood
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DOI：
10.1212/wnl.0b013e31820e7b25
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发表时间：
2011-03-01
期刊：
影响因子：
9.9
通讯作者：
Pihko, H.
中科院分区：
文献类型：
--
作者：
Isohanni, P.;Hakonen, A. H.;Pihko, H.
目的：线粒体DNA聚合酶γ（POLG 1）突变在儿童中通常表现为阿尔珀斯综合征，而在成人中，常见的表现是线粒体隐性共济失调综合征（MIRAS）伴严重癫痫。由于一些MIRAS患者在儿童时期就已经表现出共济失调或癫痫，我们在儿童时期的神经系统表现中寻找POLG 1突变。方法：我们调查了136名儿童的POLG 1，所有临床怀疑患有线粒体疾病，具有以下一种或多种情况：共济失调、轴突神经病、无已知癫痫综合征的重度癫痫、癫痫性脑病、脑肝病，结果：7例患者存在POLG 1基因突变，均伴有严重脑病和难治性癫痫。4例患者在暴露于丙戊酸钠后死亡。脑MRI显示顶枕或丘脑高信号病变、白色异常和萎缩。肌肉组织学和线粒体生化结果均正常。结论：POLG 1分析应属于第一线的DNA诊断测试的儿童脑炎样表现演变成癫痫性脑病与肝脏受累（阿尔珀斯综合征），即使脑MRI和形态，呼吸链活动，和骨骼肌中的线粒体DNA的量是正常的。在具有典型表型的儿科患者中，应在丙戊酸盐治疗前进行POLG 1分析。然而，POLG 1并不是儿童孤立性癫痫或共济失调的常见原因。神经病学（R）2011;76：811-815
Objective: Mitochondrial DNA polymerase gamma (POLG1) mutations in children often manifest as Alpers syndrome, whereas in adults, a common manifestation is mitochondrial recessive ataxia syndrome (MIRAS) with severe epilepsy. Because some patients with MIRAS have presented with ataxia or epilepsy already in childhood, we searched for POLG1 mutations in neurologic manifestations in childhood.Methods: We investigated POLG1 in 136 children, all clinically suspected to have mitochondrial disease, with one or more of the following: ataxia, axonal neuropathy, severe epilepsy without known epilepsy syndrome, epileptic encephalopathy, encephalohepatopathy, or neuropathologically verified Alpers syndrome.Results: Seven patients had POLG1 mutations, and all of them had severe encephalopathy with intractable epilepsy. Four patients had died after exposure to sodium valproate. Brain MRI showed parieto-occipital or thalamic hyperintense lesions, white matter abnormality, and atrophy. Muscle histology and mitochondrial biochemistry results were normal in all.Conclusions: POLG1 analysis should belong to the first-line DNA diagnostic tests for children with an encephalitis-like presentation evolving into epileptic encephalopathy with liver involvement (Alpers syndrome), even if brain MRI and morphology, respiratory chain activities, and the amount of mitochondrial DNA in the skeletal muscle are normal. POLG1 analysis should precede valproate therapy in pediatric patients with a typical phenotype. However, POLG1 is not a common cause of isolated epilepsy or ataxia in childhood. Neurology (R) 2011;76:811-815