摘要
目的 研究线粒体呼吸链复合物活性缺陷导致心脏损害患儿的临床、生化和基因特点.方法 3例患儿分别于8、4、3岁时因心律失常和心脏增大,于2009年1月至2012年5月在北京大学第一医院就诊.经过生化、尿有机酸分析、血氨基酸与酯酰肉碱谱分析、溶酶体酶活性测定等检查排除了炎症、免疫性疾病及氨基酸、有机酸、脂肪酸、溶酶体代谢病导致的心脏疾病.采用外周血白细胞分光光度法测定线粒体呼吸链酶复合物活性,并进行线粒体全基因序列分析.结果 2例为肥厚型心肌病；心功能Ⅰ～Ⅱ级.1例为心律失常；心功能Ⅰ级.血清磷酸肌酸激酶、肌酸激酶同工酶增高.3例患儿均有不同类型的线粒体呼吸链酶复合物活性缺陷,例1为呼吸链复合物Ⅲ和Ⅴ缺陷,复合物Ⅰ＋Ⅲ活性18.7 nmol/（min·mg线粒体总蛋白）,复合物Ⅴ活性20.4 nmol/（min·mg线粒体总蛋白）.线粒体基因分析显示tRNAGluA14693G突变,D-loop区T16519C突变.例2为单纯呼吸链复合物Ⅰ缺陷,活性为22.0 nmol/（min·mg线粒体总蛋白）.D-loop区A16183C、T16189C、G15043A突变.例3为呼吸链复合物Ⅳ和Ⅴ缺陷,分别是21.0 nmol/（min·mg线粒体总蛋白）和23.2 nmol/（min·mg线粒体总蛋白）.D-loop区C253T、C16187T突变.单倍型分析3例患儿均属H2a2a.结论 表现为心脏损害的线粒体病临床上可表现为心肌病、心律失常等,有多种线粒体呼吸链复合物缺陷类型,线粒体基因tRNAGlu A14693G突变为病因之一.
Objective Mitochondrial disease is a group of energy metabolic disorders, characterized by involvement of muhisystem with high energy requirements. Encephalomyopathies are common clinical findings of the mitochondrial diseases. However, mitochondrial cardiac damage is not rare. In this study, the clinical, biological, and genetic analyses were performed in three patients with mitochondrial cardiac damage, in order to understand the characteristics of mitochondrial diseases. Method Three girls presented with arrhythmia and cardiac enlargement from the age of 3, 4 and 8 years respectively. They were admitted into the Peking University First Hospital. Infection, autoimmune diseases, aminoacidopathies, organic acidurias, mitochondrial-fatty acid oxidation defects, and lysosomal storage disease were excluded by routine laboratory examinations and metabolic analysis for blood amino acids, acylcarnitines, urinary organic acids, and lysosome activity assay. Peripheral leukocytes mitochondrial respiratory chain enzyme I to V activities were measured by spectrophotometry. The entire sequence of the mitochondrial DNA was analyzed. Result In two patients （ case 1 and case 3 ）, hypertrophic cardiomyopathy and grade I to grade Ⅱ of cardiac function were found. One patient （case 2） was diagnosed with arrhythmia and grade I of cardiac function. Increased creatine phosphokinase and creatine kinase isoenzyme MB were observed. Mitochondrial respiratory chain complex deficiencies were indentified in the three patients. Patient 1 had combined deficiencies of complex HI and V. The activity of complex Ⅰ ＋Ⅲ was 18. 7 nmol/（min · mg mitochondrial protein） （control 84. 4 ± 28. 5 ）. The activity of complex V was 20. 4 nmol/（ min · mg mitochondrial protein） （control 103.7 ± 29. 2）. In her mitochondrial gene, A14693G on tRNAGlu and T16519C on D-loop werefound. Patient 2 had an isolated complex [ deficiency. The activity was 22. 0 nmol/（ min ~ mg mitochondrial protein） （control 44. 0 ＋ 5.4）. A1618
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2013年第12期909-914,共6页
Chinese Journal of Pediatrics
基金
＂十二五＂国家科技支撑计划项目（2012BAI09B04）
博士后基金（2013M532107）
关键词
心肌疾病
线粒体疾病
电子转运
基因
线粒体
Cardiomyopathies
Mitochondrial diseases
Electron transport
Genes, mitochondrial
