Screening for tetrahydrobiopterin deficiency among hyperphenylalaninemia patients in Southern China  

中国南方高苯丙氨酸血症者中四氢生物蝶呤缺乏症的筛查(英文)

作　　者：叶军[1] 刘哓青[1] 马燮琴[2] 张雅芬[1] 黄哓东 陈瑞冠[1] 顾学范[1] 

机构地区：[1]上海第二医科大学附属新华医院,上海市儿科医学研究所小儿内分泌遗传代谢病室,上海200092 [2]广州市妇婴医院新生儿筛查中心,广州510180

出　　处：《Chinese Medical Journal》2002年第2期57-61,151-152,共7页中华医学杂志（英文版）

基　　金：theShanghaiScientificandTechnologyCommittee (No .95 41190 3)

摘　　要：Abstract Objectives To assess the incidence of tetrahydrobiopterin (BH4)deficiency among patients with hyperphenylalaninemia (HPA) in southern Chinese and evaluate clinical outcome and gene mutations in tetrahydrobiopterin deficient patients.Methods Urinary neopterin (N) and biopterin (B) was analyzed in 87 patients with hyperphenylalaninemia by high-performance liquid chromatography. Further combined loading tests with phenylalanine(Phe) (100*!mg/kg) and tetrahydrobiopterin (BH4) (7.5*!mg/kg) were performed in suspected patients with abnormal urinary pterin profiles. Gene mutation analysis was performed for patients with BH4 deficiency and their parents. BH4 deficient patients were treated with BH4 and neurotransmitter precursors after diagnosis. Blood phenylalanine levels, clinical symptoms and mental development were followed up.Results Eleven patients were diagnosed as having BH4 deficiency caused by 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency. The incidence of tetrahydrobiopterin (BH4) deficiency among patients with hyperphenylalaninemia (HPA) in southern Chinese was 10%. Combined loading tests with phenylalanine and oral BH4 were done in 4 of 11 patients and their phenylalanine levels were decreased to normal 4-6h after BH4 administration. Four different mutations (P87S, N52S, D96N and G144R) in the PTPS gene were detected in 5 families. Five PTPS-deficient patients were treated with synthetic BH4, neurotransmitter precursors (L-dopa plus carbidopa, and 5-hydroxytryptophan). They had satisfactory physical and mental development after treatment. One patient with partial PTPS deficiency had normal growth and mental development without treatment. Conclusions Our results emphasize that screening for BH4 deficiency should be carried out in all patients with hyperphenylalaninemia in order to minimize the misdiagnosis. Patients with BH4 deficiency should be treated early with BH4 and a combination of neurotransmitter precursors.目的　得出我国南方高苯丙氨酸血症 (HPA)者中四氢生物蝶呤 (BH4 )缺乏症发病率及总结BH4缺乏症者基因研究和临床转归。方法　应用高效液相层析仪对 87例高苯丙氨酸血症者进行尿新蝶呤 (N)和生物蝶呤 (B)分析 ;对尿蝶呤异常者进一步作苯丙氨酸 (Phe) (10 0mg/kg)及BH4 (7 5mg/kg)联合负荷试验。对BH4缺乏症者及父母进行基因突变检测。BH4缺乏者一经诊断后立即接受BH4及神经递质前质治疗 ,追踪随访患者的血Phe浓度、临床症状及智能发育。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 ,得出中国南方高苯丙氨酸血症者中BH4缺乏症的发病率为 10 %。 11例中 4例作了苯丙氨酸及BH4联合负荷试验 ,在口服四氢生物蝶呤后 4 - 6小时 ,他们的血苯丙氨酸水平降至正常。从 5个PTPS缺乏症者家系中发现 4种PTPS基因突变类型 ,即P87S、N5 2S、D96N及G144R。 5例PTPS缺乏症患者经BH4、神经递质前质L DOPA、卡比多巴及 5 羟色氨酸治疗后 ,体格发育和智能发育令人满意。 1例部分性PTPS缺乏者未经治疗 ,其生长发育和智能发育接近正常。结论　对所有高苯丙氨酸血症者必须进行BH4缺乏症的筛查 ,以降低误诊率。BH4缺乏症者应尽早接受BH4及神经递质前质联合治疗。

关 键 词：phenylketonuria   ·   gene mutation   ·   neonatal screening  ·   tetrahydrobiopterin deficiency 

分 类 号：R725.8[医药卫生—儿科]