CAJ | 학술논문

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) (100mg/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、N52S、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。
목적　득출아국남방고분병안산혈증(HPA)자중사경생물접령(BH4)결핍증발병솔급총결BH4결핍증자기인연구화림상전귀。 방법　응용고효액상층석의대87례고분병안산혈증자진행뇨신접령(N)화생물접령(B)분석；대뇨접령이상자진일보작분병안산(Phe) (100mg/kg)급BH4(7.5mg/kg)연합부하시험。대BH4결핍증자급부모진행기인돌변검측。BH4결핍자일경진단후립즉접수BH4급신경체질전질치료，추종수방환자적혈Phe농도、림상증상급지능발육。 결과　11례진단위6-병동선사경접령합성매(PTPS)결핍소치BH4결핍증，득출중국남방고분병안산혈증자중BH4결핍증적발병솔위10%。11례중4례작료분병안산급BH4연합부하시험，재구복사경생물접령후4-6소시，타문적혈분병안산수평강지정상。종5개PTPS결핍증자가계중발현4충PTPS기인돌변류형，즉P87S、N52S、D96N급G144R。5례PTPS결핍증환자경BH4、신경체질전질L-DOPA、잡비다파급5-간색안산치료후，체격발육화지능발육령인만의。1례부분성PTPS결핍자미경치료，기생장발육화지능발육접근정상。 결론　대소유고분병안산혈증자필수진행BH4결핍증적사사，이강저오진솔。BH4결핍증자응진조접수BH4급신경체질전질연합치료。
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) (7.5mg/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.