Analysis of the Mitochondrial Complex I-V Enzyme Activities of Peripheral Leukocytes in Oxidative Phosphorylation Disorders
Analysis of the Mitochondrial Complex I-V Enzyme Activities of Peripheral Leukocytes in Oxidative Phosphorylation Disorders
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DOI：
10.1177/0883073811399905
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发表时间：
2011-08-01
影响因子：
1.9
通讯作者：
Yang, Yan-Ling
中科院分区：
文献类型：
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作者：
Ma, Yan-Yan;Zhang, Xue-Lin;Yang, Yan-Ling
线粒体氧化磷酸化缺陷是线粒体疾病的常见原因，其特征在于多器官受累和临床表现的异质性。由于缺乏临床上可行的方法，诊断很困难。在这项研究中，线粒体复合物I-V酶活性测定64例疑似线粒体疾病和200名健康对照。采用分光光度法测定外周血白细胞线粒体复合物I-V酶活性。诊断是基于临床表现，磁共振成像（MRI），肌肉病理学和线粒体DNA点突变筛查。对氨基酸病、有机酸尿症和脂肪酸β-氧化缺陷进行了鉴别诊断。35例（54.7%）患者根据特征性脑MRI诊断为Leigh综合征。发现对照中的复合酶活性是稳定的。29例（45.3%）患者存在氧化磷酸化缺陷。20例（31.2%）患者存在孤立性复合物缺陷，复合物I缺陷（n = 2，3.1%）、复合物II缺陷（n = 3，4.7%）、复合物III缺陷（n = 5，7.8%）、复合物IV缺陷（n = 5，7.8%）和复合物V缺陷（n = 5，7.8%）。9例患者被发现有复合缺陷，3（4.7%）有复合物I和IV的联合缺陷，2（3.1%）有复合物III和V的联合缺陷，2（3.1%）有复合物I和V的联合缺陷。总之，外周血白细胞氧化磷酸化酶活性测定被认为是一种可靠的方法，用于诊断线粒体疾病。
Mitochondrial oxidative phosphorylation defects are a common cause of mitochondrial diseases, which are characterized by multiorgan involvement and clinically heterogeneous manifestations. Diagnosis is difficult because of the lack of clinically feasible methods. In this study, mitochondrial complex I-V enzyme activity was measured in 64 patients with suspected mitochondrial disease and 200 healthy controls. Spectrophotometric assay was used for the analysis of mitochondrial complex I-V enzyme activity in peripheral leukocytes. Diagnosis was based on clinical presentation, magnetic resonance imaging (MRI), muscle pathology, and point mutation screening in mitochondrial DNA. The differential diagnosis of aminoacidopathies, organic acidurias, and fatty acid beta-oxidation defects was made. Thirty-five patients (54.7%) were diagnosed with Leigh syndrome based on characteristic brain MRI. Complex enzyme activity in controls was found to be stable. A deficiency in the oxidative phosphorylation was found in 29 patients (45.3%). Twenty (31.2%) patients had isolated complex defects, complex I deficiency (n = 2, 3.1%), complex II deficiency (n = 3, 4.7%), complex III deficiency (n = 5, 7.8%), complex IV deficiency (n = 5, 7.8%), and complex V deficiency (n 5, 7.8%). Nine patients were found to have combined deficiencies, 3 (4.7%) had combined deficiencies of complex I and IV, 2 (3.1%) had combined deficiencies of complex III and V, and 2 (3.1%) had a combined deficiency of complex I and V. In conclusion, the peripheral leukocyte oxidative phosphorylation enzyme activity assay was found to be a reliable method for the diagnosis of mitochondrial diseases.