Hamano H, Ohta T, Takekawa Y, Kouda K, Shinohara Y
Department of Neurology, Tokai University School of Medicine.
Rinsho Shinkeigaku. 1997 Oct;37(10):917-22.
We report a 56-year old female with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), presenting with protein-losing gastroenteropathy and serum copper deficiency. There was no neuromuscular disease in her family members. Three years prior to admission, she developed severe gastrointestinal symptoms including diarrhea, nausea, vomiting and ascites, and was diagnosed as having protein-losing gastroenteropathy based on alpha(1)-antitrypsin clearance and other tests. She was referred to our department when neurological symptoms were apparent. Neurological examinations revealed bilateral ptosis, ophthalmoplegia, hearing loss, facial and limb muscle weakness, mild sensory deficit of vibration on her feet and hypoactive deep tendon reflexes. Pigmentary retinopathy, cerebellar ataxia and heart block were not seen. Serum copper level was decreased to 45 micrograms/dl (normal: 83-155). Chronic intestinal pseudo-obstruction was proven by X-ray studies, and diffuse leukoencephalopathy demonstrated on brain MRI. On EMG, motor nerve conduction velocities were prolonged with temporal dispersion. Her muscle biopsy from biceps brachii muscle showed both neuropathic and myopathic changes, scattered ragged-red fibers and focal cytochrome c oxidase deficiency. Southern blot and polymerase chain reaction analysis on mitochondrial DNA showed no deletions nor point mutations. The clinical and pathologic findings of the present patient fulfilled the diagnostic criteria of mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) proposed by Hirano et al. There are few reported patients with MNGIE in Japan, but none presented with protein-losing gastroenteropathy and serum copper deficiency. Since the copper is a cofactor of cytochrome c oxidase, decreased serum copper level may aggravate the respiratory chain enzyme metabolism in mitochondria. Therefore, treatment for gastrointestinal tract disturbance and copper administration may be necessary to prevent disease progression.
我们报告了一名56岁的女性，患有线粒体神经胃肠性脑肌病（MNGIE），表现为蛋白丢失性胃肠病和血清铜缺乏。她的家庭成员中没有神经肌肉疾病。入院前三年，她出现了严重的胃肠道症状，包括腹泻、恶心、呕吐和腹水，并根据α1抗胰蛋白酶清除率和其他检查被诊断为蛋白丢失性胃肠病。当出现神经症状时，她被转诊至我们科室。神经检查发现双侧上睑下垂、眼肌麻痹、听力丧失、面部和肢体肌肉无力、足部轻度振动觉感觉减退以及腱反射减弱。未发现色素性视网膜病变、小脑共济失调和心脏传导阻滞。血清铜水平降至45微克/分升（正常：83 - 155）。X线检查证实存在慢性肠道假性梗阻，脑MRI显示弥漫性白质脑病。肌电图显示运动神经传导速度延长且有时间离散。她肱二头肌的肌肉活检显示既有神经病变又有肌病改变，散在的破碎红纤维和局灶性细胞色素c氧化酶缺乏。线粒体DNA的Southern印迹和聚合酶链反应分析未发现缺失或点突变。本患者的临床和病理表现符合Hirano等人提出的线粒体神经胃肠性脑肌病（MNGIE）的诊断标准。在日本，报道的MNGIE患者很少，但没有出现蛋白丢失性胃肠病和血清铜缺乏的情况。由于铜是细胞色素c氧化酶的辅助因子，血清铜水平降低可能会加重线粒体呼吸链酶的代谢。因此，可能需要治疗胃肠道紊乱并补充铜以防止疾病进展。
