高苯丙氨酸血症患儿尿蝶呤谱分析及正常人群尿蝶呤谱参考区间的建立  

Analysis of urinary pterin in children with hyperphenylalanineemia and establishment of reference range of urinary pterin in normal population

作　　者：曾伟宏[1] 江剑辉[1] 欧阳海梅[1] 谢汛杰 梁金群[1] 陈暖[1] 刘舒[1] 韦思思 严莹 陈丽莹 吴爱武 ZENG Wei-hong;JIANG Jian-hui;OUYang Hai-mei;XIE Xun-jie;LIANG Jin-qun;CHEN Nuan;LIU Shu;WEI Si-si;YAN Ying;CHEN Li-ying;WU Ai-wu(Children Inherit Metabolism and Endocrine Department, Guangdong Women and Children＇ s Hospital, Guangzhou Medical University, Guangzhou Guangdong 511442, China;KingMed School of Laboratory Medicine , Guangzhou Medical University, Guangzhou Guangdong 510182 , 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,广州511442 [2]广州医科大学金域检验学院,广州510182

出　　处：《中国优生与遗传杂志》2018年第6期5-9,共5页Chinese Journal of Birth Health & Heredity

基　　金：广东省医学科学技术研究基金(A2017305)

摘　　要：目的探讨尿蝶呤谱分析、口服四氢生物蝶呤(tetrahydrobiopterin,BH_4)药物负荷试验及酸学分析在高苯丙氨酸血症(hyperphenylalaninemia,HPA)诊断与分型中的意义,同时建立本地区正常人群尿蝶呤谱参考区间,为我国正常人群尿蝶呤谱参考区间的制订提供可靠数据。方法 2014年1月至2017年6月本中心正常健康人群及无先天性遗传代谢缺陷的人群859例为正常对照组,确诊的137例高苯丙氨酸血症患者为研究组,运用串联质谱(LC-MS/MS)测定血苯丙氨酸(Phe)、高效液相色谱(HPLC)对尿液蝶呤谱分析,同时根据BH_4药物负荷试验,红细胞二氢生物蝶啶还原酶(DHPR)进行分组研究,运用统计学进行差异性分析及正常人群各年龄段参考区间建立。结果 137例HPA中,BH_4反应型HPA22例,占16.05%(22/137),无反应型HPA79例,占57.66%(79/137),BH_4缺乏症36例,占26.27%(36/137),其中6-丙酮酰四氢蝶呤合成酶(6-pyruvoyl tetrahydropterin synthase deficiency,PTPS)34例,占BH_4缺乏症94.44%(34/36)例,二氢生物蝶啶还原酶(dilydropterindine reductase deficiency,DHPR)2例,占5.56%(2/36)。尿蝶呤谱PTPS缺乏组年龄差异无统计学意义(P>0.05),新蝶呤(neopterin,N)高于正常对照组和无反应型HPA组,生物蝶呤(biopterin,B)及生物蝶呤百分比(B/N+B,B%)明显低于各组,差异有统计学意义(P<0.05);BH_4反应型HPA和无反应型HPA组N、B均高于正常对照组,差异有统计学意义(P<0.05),而B%差异无统计学意义(P>0.05);BH_4反应型HPA与无反应型HPA两组差异无统计学意义(P>0.05)。口服BH_4药物负荷试验PTPS组血Phe浓度下降最快并在4h内降至正常,无反应型HPA组24h变化不明显,BH_4反应型HPA和DHPR缺乏组下降速度和幅度相似,但DHPR缺乏组酶活性低于正常。结论尿蝶呤谱分析对BH_4缺乏症分型及鉴别BH_4反应型HPA、无反应型HPA有辅助作用。口服BH_4药物负荷试验能快速判断血Phe对BH_4反应程度、血Phe的变化趋势,为可为HPA患者�Objective：To explore the significance of urinary pterin analysis,oral tetrahydrobiopterin（BH4）drug load test and acid analysis in the diagnosis and typing of hyperphenylalanineemia,and to establish the normal the reference range of urinary pterin would be provide reliable evidence for the development of the reference range of urinary pterin in our country. Methods：From January 2014 to June 2017,859 patients with normal healthy and no congenital genetic metabolic defects were normal control group. 137 patients with hyperphenylalanineemia（HPA）diagnosed by our center were the study group,hyperphenylalaninemia（Phe）was determined by tandem mass spectrometry（LC-MS/MS）,and the urinary protein was analyzed by high performance liquid chromatography（HPLC）. At the same time,according to the BH4 drug load test,erythrocyte dihydrobiopanin reductase（DHPR）for group study,using statistical analysis of differences and the normal population of the age range of reference to develop. Results：137 cases of HPA,BH4-reactive HPA 22 cases,accounting for 16.05%（22/137）,non-reactive HPA79 cases,accounting for 57.66%（79/137）,BH4 deficiency in 36 cases,accounting for 26.27%（36/137）. Among them,34 cases of 6-pyruvoyl tetrahydropterin synthase deficiency（PTPS）,accounting for 94.44%（34/36）of BH4 deficiency,2 cases of dilydropterindine reductase deficiency（DHPR）,accounting for 5.56%（2/36）. Urinay pterins of PTPS lack of age difference was not statistically significant（P〉0.05）,the neopterin,（N）of PTPS lack group higher than the normal control group and non responsiveness HPA group and biopterin（B）and biopterin percentage（B/N ＋ B,B%）significantly lower than the other groups,the difference was statistically significant（P〈0.05）;The N and B of the BH4 reaction type HPA and the reactive HPA group were higher than the normal control group,and the difference was statistically significant（P〈0.05）,while the difference in B% was not statistically significant（P〉0.0

关 键 词：高苯丙氨酸血症 尿蝶呤谱 BH4药物负荷试验 参考区间 

分 类 号：R722.11[医药卫生—儿科]