中国南方四氢生物蝶呤缺乏症筛查、临床及基因突变的系列研究  

Studies on neonatal screening, clinical and gene analysis for tetrahydrobiopterin deficiency in Southern Chinese

作　　者：叶军[1] 刘晓青[1] 马燮琴[2] 黄晓东[1] 张雅芬[1] 顾学范[1] 陈瑞冠[1] 

机构地区：[1]上海市儿科医学研究所,200092 [2]广州市妇婴医院新生儿筛查中心

出　　处：《中华医学遗传学杂志》2001年第2期92-95,共4页Chinese Journal of Medical Genetics

基　　金：上海市科学发展基金重点项目!(9541 1 90 31 )&&

摘　　要：目的　得出我国南方高苯丙氨酸血症 (hyperphenylalaninemia,HPA)者四氢生物蝶呤(tetrahydrobiopterin,BH4)缺乏症的发病率 ,总结 BH4缺乏症者基因突变和临床转归的研究。方法　对87例 HPA者做尿新蝶呤 (N)和生物蝶呤 (B)分析 ;对 BH4缺乏症者进行基因突变检测及治疗随访。结果11例诊断为 6 -丙酮酰四氢蝶呤合成酶 (PTPS)缺乏所致 BH4缺乏症 ,其尿 N/ B>38,B% <5 % ,在 HPA中其发病率为 12 %。 5例中发现 4种 PTPS基因突变类型 ,即 P87S、N5 2 S、D96 N及 G144 R(新突变类型 )。5例经 BH4、L- DOPA及 5 -羟色氨酸治疗后体格发育良好 ,4例智商 (IQ) 70～ 80分。结论　对所有 HPA者需进行 BH4缺乏症的筛查 ,以降低误诊率。Objective: To find out the incidence of tetrahydrobiopterin deficiency (BH4D) among patients with hyperphenylalaninemia in Southern Chinese and evaluate the clinical outcome and gene mutations of tetrahydrobiopterin deficient patients. Methods: Analyses of urinary neopterin (N) and biopterin (B) were done in 87 patients with hyperphenylalaninemia by high-performance liquid chromatography. The patients with BH4 deficiency and their parents were asked to undergo the gene mutation analysis and the patients were treated and followed up. Results: Eleven cases of which the urinary N/B ratio was higher than 38 and B% lower than 5% were diagnosed as BH4 deficiency caused by 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. The incidence of BH4 deficiency among patients with hyperphenylalaninemia is 12% in Southern Chinese. PTPS gene mutations (P87S, N52S, D96N and G144R) were detected from 5 PTPS deficient families. The G144R mutation is a new mutation. The five PTPS-deficient patients were treated with synthetic BH4, neurotransmitter precursors L-dopa and 5-hydroxytryptophan. They had satisfactory physical and mental development after treatment, and 4 of them scored their IQ 70-80. Conclusion: The screening for BH4 deficiency should be carried out in all patients with hyperphenylalaninemia in order to minimize the misdiagnoses.

关 键 词：苯丙酮尿症 四氢生物蝶呤缺乏症 基因突变 新生儿筛查 遗传代谢病 

分 类 号：R722.11[医药卫生—儿科]