Martikainen Mika H, Hinttala Reetta, Majamaa Kari
Department of Neurology, Turku University Hospital, Turku, Finland.
BMJ Case Rep. 2010 Sep 29;2010:bcr0120102604. doi: 10.1136/bcr.01.2010.2604.
Mutations in POLG1 are an important cause of human mitochondrial disease. We describe a woman who presented with bilateral ptosis and external ophthalmoplegia at 64 years of age. Neurological examination revealed symptoms of diffuse encephalopathy. The symptoms were progressive and at 67 years she was severely cognitively impaired, had severe bilateral ptosis and complete external ophthalmoplegia. Frequent cytochrome c oxidase-negative fibres were detected in muscle. Electrophysiological examination revealed myopathic changes and axonal neuropathy. Standard laboratory tests were normal. Brain CT showed general, moderate cortical atrophy. Molecular analysis of muscle DNA revealed multiple mitochondrial DNA deletions. Sequencing of the entire POLG1 gene revealed two changes c.2993C>T (p.998S>L) and c.3550G>C (p.1184D>H). Both mutations are previously unreported and confirmed to be compound heterozygous. Late-onset progressive external ophthalmoplegia with severe encephalopathy is an unusual combination in patients with POLG1 mutations. POLG-associated disease should be considered in any patient with unexplained or unusual neurological features.
POLG1基因突变是人类线粒体疾病的一个重要病因。我们描述了一位64岁出现双侧上睑下垂和眼球外肌麻痹的女性。神经系统检查发现弥漫性脑病症状。症状呈进行性发展，67岁时她出现严重认知障碍、严重双侧上睑下垂和完全性眼球外肌麻痹。肌肉中检测到频繁的细胞色素c氧化酶阴性纤维。电生理检查显示肌病改变和轴索性神经病。标准实验室检查结果正常。脑部CT显示广泛性中度皮质萎缩。肌肉DNA的分子分析显示多个线粒体DNA缺失。对整个POLG1基因进行测序发现两个变化，即c.2993C>T（p.998S>L）和c.3550G>C（p.1184D>H）。这两个突变此前均未报道，且被确认为复合杂合突变。伴有严重脑病的迟发性进行性眼球外肌麻痹在POLG1突变患者中是一种不寻常的组合。对于任何具有无法解释或不寻常神经特征的患者，都应考虑POLG相关疾病。
