高苯丙氨酸血症分型和代谢谱分析  

Analysis of types and metabolic profiles of hyperphenylalaninemia

作　　者：曾伟宏[1] 吴爱武 谢汛杰 欧阳海梅[1] 梁金群[1] 陈暖[1] 刘舒[1] 韦思思 陈丽莹 江剑辉[1] Zeng Weihong 1, Wu Aiwu2, Xie Xunjie1 , Ouyang Haimei1 ,Liang Jinqun1, Chen Nuan1,Liu Shu1, Wei Sisi1, Chen Liying1,Jiang Jianhui1(1Department of Pediatric Inherit Metabolism and Endocrine, Guangdong Women and Children＇s Hospital, Guangzhou Medical University, Guangzhou 511442, China;2 Kingmed School of Laboratory Medicine, Guangzhon Medical University, Guangzhou 510182, Chin)

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,511442 [2]广州医科大学金域检验学院,510182

出　　处：《中华实用儿科临床杂志》2018年第8期572-575,共4页Chinese Journal of Applied Clinical Pediatrics

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）各种类型发病特点和血液、尿液代谢指标谱差异及其相互关系.方法 选择2014年1月至2017年6月在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确诊的137例HPA患儿,通过血液串联质谱（MS/MS）、尿液气相色谱质谱（GC-MS）和高效液相色谱（HPLC）对患儿血液、尿液代谢物浓度分析,同时根据四氢生物蝶呤（BH4）药物负荷试验、红细胞二氢生物蝶啶还原酶活性进行分组,根据各组HPA代谢物浓度运用统计学进行差异性分析及相关性分析.结果 137例HPA患儿中,苯丙氨酸（Phe）羟化酶（PAH）缺乏症101例（73.7％）,其中经典型苯丙酮尿症（PKU） 21例（15.3％）,轻度PKU 37例（27.0％）,轻度HPA 43例（31.4％）;BH4反应型22例（16.1％）,BH4无反应型79例（57.7％）;四氢生物蝶呤缺乏（BH4D）36例（26.3％）,其中6-丙酮酰四氢蝶呤合成酶（PTPS）缺乏症34例（24.8％）,二氢生物蝶啶还原酶（DHPR）缺乏症2例（1.5％）.各型血Phe水平与尿苯乙酸（r=0.673,P＜0.01）、苯乳酸（r=0.736,P＜0.01）、苯丙酮酸（r=0.642,P＜0.01）显著相关,与新蝶呤（N）（r=0.442,P ＜0.01）、生物蝶呤（B）（r =0.398,P ＜0.01）低度相关;尿苯乙酸、苯乳酸、苯丙酮酸与尿蝶呤无相关性.尿蝶呤谱PTPS缺乏组、BH4反应型、BH4无反应型比较差异均有统计学意义（均P＜0.05）,BH4反应型与BH4无反应型组差异无统计学意义（P＞0.05）.结论 通过分析不同类型的HPA代谢谱,掌握本地区发病情况和特征,HPA患儿血Phe一定浓度区间内尿苯乙酸、苯乳酸、苯丙酮酸可呈阴性,不宜单独使用GC-MS筛查HPA.尿蝶呤谱分析对BH4D分型及鉴别BH4反应型、BH4无反应型PKU有辅助作用,掌握各型HPA代谢指标浓度及相关性,可为HPA早期诊断、精确治疗、随访提供依据.Objective To study the characteristics of hyperphenylalaninemia （HPA） and the differences in blood and urine metabolic index and their correlation.Methods A total of 137 patients with HPA diagnosed by the Pediatric Inherit Metabolism and Endocrine Department,Guangdong Women and Children＇s Hospital,Guangzhou Medical University from January 2014 to June 2017,were enrolled.Tandem mass spectrometry （MS/MS）,gas chromatography/ mass spectrometry （GC-MS） and high performance liquid chromatography （HPLC） were used to analyze the concentration of blood and urine metabolites in children,and the patients were divided into different groups according to the drug load test of tetrahydrobiopterin （BH4） and dihydrobiopterindine reductase （DHPR） deficiency.The HPA metabolite analysis of horizontal concentration by statistical differences and correlation analysis were performed.Results Among the 137 cases of HPA,there were 101 cases （73.7%） of phenylalanine hydroxylase deficiency （PAH）,and among them 21 cases （15.3%） were classic phenylketonuria （PKU）,37 cases were mild PKU （27.0%）,43 cases （31.4%） wcrc mild HPA.Thcrc were 22 cases （16.1%） with BH4 reaction,and 79 cases （57.7%） of non-reactive type.Besides,there were 36 cases （26.3%） of tetrahydrobiopterin deficiency （BH4 D）,of which 6-pyruvoyl tetrahydropterin synthase deficiency （PTPS） in 34 cases （24.8%） and dihydrobiopterindine reductase deficiency （DHPR） in 2 cases （1.5%）.Urinary phenylacetic acid （r =0.673,P 〈 0.01）,phenyllactic acid （r =0.736,P 〈 0.01）,phenylpyruvic acid （r =0.642,P 〈 0.01） were significantly correlated with blood phenylalanine （Phe） concentration,and the neopterin （N） （r =0.442,P 〈 0.01） and biopterin （B） （r =0.398,P 〈 0.01） had low correlation.Urinary phenylacetic acid,phenyllactic acid and phenylpyruvic acid had no correlation with urinary pterin.There were significant differences among PTPS deficiency group,BH4 response type,and no

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

分 类 号：R725.8[医药卫生—儿科]