血液3-羟基异戊酰肉碱增高的遗传代谢疾病分析及其阈值的建立  

Analysis of genetic metabolic diseases with increased C5-OH acylarnitine and the establishment of its cut-off values

作　　者：曾伟宏[1] 欧阳海梅[1] 谢汛杰 袁莹 梁金群[1] 陈暖[1] 刘舒[1] 韦思思 陈丽莹[1] 江剑辉[1] ZENG Wei-hong;OUYANG Hai-mei;XIE Xun-jie;YUAN Ying;LIANG Jin-qun;CHEN Nuan;LIUShu;WEI Si-si;CHEN Li-ying;JIANG Jian-hui(Children Inherit Metabolism and Endocrine Department,Guangdong Women and Children＇s Hospital,Guangzhou 511442,Guangdong,China)

机构地区：[1]广东省妇幼保健院儿童遗传代谢与内分泌科,广东广州511442

出　　处：《广东医学》2018年第19期2885-2889,共5页Guangdong Medical Journal

基　　金：国家重点研发计划子课题(编号:2016YFC1000307-15);广东省医学科研基金项目(编号:A2017305)

摘　　要：目的探讨分析血液3-羟基异戊酰肉碱(C5-OH)增高的遗传代谢病类型、代谢指标及临床表现,并通过受试者工作特征(ROC)曲线法,评价串联质谱(LC-MS/MS)技术非衍生法对C5-OH增高疾病诊断价值并建立本中心C5-OH的阈值。方法选取确诊患儿20例为阳性组,正常健康儿童281例为正常对照组,通过LC-MS/MS测定血液C5-OH浓度,气相色谱质谱(GC-MS)检测尿液有机酸。同时绘制ROC曲线,确定C5-OH的最佳阈值。结果确诊3-甲基巴豆酰辅酶A羧化酶缺乏症6例,多种羧化酶缺乏症8例,甲基丙二酸2例,多种酰基辅酶A脱氢酶缺乏症1例,中链酰基辅酶A脱氢酶缺乏症1例,3-甲基戊烯二酸尿症1例,肝豆状核变性合并糖原贮积症Ⅸ1例。阳性组血液C5-OH浓度显著高于正常对照组,差异有统计学意义(P <0. 01);血液C5-OH ROC曲线下面积为0. 937,最佳阈值为0. 769μmol/L,敏感度和特异度分别为95. 00%、80. 07%。结论 3-甲基巴豆酰辅酶A羧化酶和多种羧化酶缺乏症是临床上最常见的血液C5-OH增高的遗传代谢病,LC-MS/MS非衍生法具有较高的诊断价值,建立最佳阈值有利于提高疾病的诊断率。Objective To study the disease types,metabolic index and clinical symptoms of genetic blood 3-hydroxyisoamylcarnitine（ C5-OH） increasing metabolic diseases; and through the receiver operating characteristic curve（ ROC）,to set up the center cutting value of the C5-OH evaluation of tandem mass spectrometry（ LC/MS/MS）. Methods Twenty cases were enrolled as research group,as 281 cases of normal healthy children were included as control group. The concentration of C5-OH in blood was determined by LC-MS/MS,and urine organic acids determined by GC-MS. At the same time,the ROC curve was drawn to determine the best cutting value of C5-OH. Results There were6 confirmed cases of 3-methylcrotonyl-coenzyme A carboxylase deficiency,8 cases of multiple carboxylase deficiency,2 cases of methyl malonic acid,1 case of multiple acyl-Co A dehydrogenase deficiency,1 case of the chain acyl coenzyme A dehydrogenase deficiency,1 case of 3-methylglutaryl urethanuria,and 1 case of hepatolenticular degeneration combined with glycogen storage product disorder Ⅸ. The concentration of blood C5-OH in the case group was significantly higher than that in the control group. The area under the curve of blood C5-OH ROC was 0. 937,and the optimal cut value was 0. 769 mol/L,with the sensitivity and specificity of 95. 00% and 80. 07%,respectively. Conclusion 3-methylcrotonyl-coenzyme A carboxylase deficiency and multiple carboxylase deficiency are the most common genetic metabolic diseases with increased C5-OH in blood. LC-MS/MS non-derivatization method has high diagnostic value,establish the best cut-off value will help improve the diagnosis of these diseases.

关 键 词：C5-OH 串联质谱 ROC曲线 阈值 

分 类 号：R725.8[医药卫生—儿科]