Vu T H, Sciacco M, Tanji K, Nichter C, Bonilla E, Chatkupt S, Maertens P, Shanske S, Mendell J, Koenigsberger M R, Sharer L, Schon E A, DiMauro S, DeVivo D C
H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases, Columbia University, New York, NY 10032, USA.
Neurology. 1998 Jun;50(6):1783-90. doi: 10.1212/wnl.50.6.1783.
We studied five new patients with mitochondrial DNA (mtDNA) depletion to better define the clinical spectrum of this disorder.
mtDNA depletion has been associated with myopathy or hepatopathy, or both, in infants and young children. Involvement of the CNS and peripheral nervous system has not been clearly established.
We reviewed the clinical course and performed morphologic, biochemical, and genetic analyses of muscle samples from five patients.
Age at onset ranged from 3 months to 5 years, and one patient survived until age 10 1/2 years. Two patients had laboratory and clinical features reminiscent of dystrophinopathy, two had evidence of brain involvement, and two had peripheral neuropathy. Muscle biopsy specimens in all patients showed abundant ragged-red fibers. Biochemistry showed cytochrome c oxidase deficiency in all patients tested and decreased activities of other respiratory chain complexes in some.
Inheritance appeared to be autosomal recessive, suggesting that mutations in nuclear DNA are responsible for mtDNA depletion. mtDNA depletion should be considered in children with mitochondrial disorders of uncertain etiology, and criteria for diagnosis are proposed.
我们研究了5例新的线粒体DNA（mtDNA）耗竭患者，以更好地界定这种疾病的临床谱。
mtDNA耗竭与婴幼儿的肌病或肝病或两者均有关。中枢神经系统和周围神经系统受累尚未明确证实。
我们回顾了5例患者的临床病程，并对其肌肉样本进行了形态学、生化和遗传学分析。
发病年龄从3个月至5岁不等，1例患者存活至10.5岁。2例患者具有类似于肌营养不良症的实验室和临床特征，2例有脑受累证据，2例有周围神经病变。所有患者的肌肉活检标本均显示大量破碎红纤维。生化检查显示，所有检测患者均存在细胞色素c氧化酶缺乏，部分患者其他呼吸链复合体活性降低。
遗传方式似乎为常染色体隐性遗传，提示核DNA突变是mtDNA耗竭的原因。对于病因不明的线粒体疾病患儿，应考虑mtDNA耗竭，并提出了诊断标准。
