高苯丙氨酸血症尿液生物标志物特征  

Analysis of urinary biomarkers of hyperphenylalaninemia

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

机构地区：[1]广州医科大学附属广东省妇儿医院儿童遗传代谢与内分泌科,广东广州511442

出　　处：《热带医学杂志》2018年第7期881-885,共5页Journal of Tropical Medicine

基　　金：广东省医学科学技术研究基金(A2017305)

摘　　要：目的探讨高苯丙氨酸血症(HPA)尿液特异性生物标志物及其相互关系。方法选取2014年1月至2017年6月期间本院正常健康儿童132例为正常对照组,另选经广东省新生儿疾病筛查中心确诊及分型137例HPA患儿为研究组,利用气相色谱质谱技术对患儿尿液有机酸分析,根据各型HPA尿液有机酸浓度水平,运用统计学进行差异性分析及相关性分析。结果 HPA患儿尿液有机酸中,苯乙酸、苯乳酸、苯丙酮酸、3-羟基苯乙酸、4-羟基苯乙酸、4-羟基苯乳酸、4-羟基苯丙酮酸、高香草酸、香草扁桃酸明显高于正常对照组,差异有统计学意义(P<0.05),联合诊断敏感度、特异度分别为61.3%、83.3%。生物标志物之间存在相关性,尿苯丙酮酸与尿苯乙酸、尿苯乳酸及尿4-羟基苯丙酮酸呈显著正相关(r=0.56、0.80、0.67,P<0.05);尿苯乳酸与尿4-羟基苯乳酸呈显著正相关(r=0.89,P<0.05)。结论 HPA患儿尿液苯丙酮酸、尿苯乳酸、尿苯乙酸具有较高的特异度,联合多项生物标志物可有效提高HPA确诊率,为疾病确诊、分型提供参考依据。Objective To study the urinary specific biomarkers of hyperphenylalanineemia（HPA）and their relationship.Methods From January 2014 to June 2017,132 normal healthy children were selected as normal control group and 137 cases of HPA children diagnosed and classified by Guangdong Provincial Neonatal Screening Center as study group.The urinary organic acids were analyzed by gas chromatography mass spectrometry（GC-MS）technique.Results In the urinary organic acids of HPA,phenylacetic acid,phenyllactic acid,phenylpyruvic acid,3-hydroxyphenylacetic acid,4-hydroxyphenylacetic acid,4-hydroxyphenyllactic acid,4-hydroxyphenylpyruvate,homovanillic and vanilmandelic levels were significantly higher than those of the normal control group（P〈0.05）.The diagnostic sensitivity and specificity were61.3% and 83.3%,respectively by combine all urinary biomarkers which analysis of HPA.Urinary phenylacetic acid（r=0.56,P〈0.05）,phenyllactic acid（r=0.80,P〈0.05） and urinary 4-hydroxyphenylpyruvate（r=0.67,P〈0.05）,urinary phenyllactic acid and urinary 4-hydroxyphenyllactic acid（r=0.89,P〈0.05）were positively correlated.Conclusion Urinary phenylpyruvic acid,phenyllactic acid and phenylacetic acid are the specific biomarkers in HPA with high specificity.The combination of multiple biomarkers can effectively improve the diagnosis rate of HPA,and provide reference for diagnosis and classification of the disease.

关 键 词：高苯丙氨酸血症 苯丙氨酸羟化酶缺乏症 四氢生物蝶呤缺乏症 有机酸 

分 类 号：R446.122[医药卫生—诊断学]