论文部分内容阅读
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。
Objective To study the genetics and clinical outcomes of tetrahydrobiopterin (BH4) deficiency in Chinese patients with hyperphenylalaninemia (HPA) and to summarize the causes of BH4 deficiency. Methods High-performance liquid chromatography (HPLC) was used to analyze urinary neopterin (N) and biopterin (B) in 87 patients with hyperphenylalaninemia. Phenylalanine (Phe) ) (10 0 mg / kg) and BH4 (75 mg / kg). BH4 deficiency and parents of gene mutation detection. Immediately after BH4 deficiency, BH4 and neurotransmitter progenitor therapy was performed, and follow-up of patients with blood Phe concentration, clinical symptoms and intellectual development were tracked. RESULTS: Eleven patients were diagnosed with BH4 deficiency due to a lack of pyruvate tetrahydropterin synthetase (PTPS), resulting in a 10% incidence of BH4 deficiency in southern Chinese patients with hyperphenylalaninemia. Four of the 11 patients underwent a combined phenylalanine and BH4 stress test. Their blood phenylalanine levels were normalized 4 to 6 hours after oral administration of tetrahydrobiopterin. Four types of PTPS gene mutations, P87S, N5 2S, D96N and G144R, were found in five families with PTPS deficiency. Five patients with PTPS deficiency developed satisfactory physical and mental development after treatment with BH4, neurotransmitter progenitor L DOPA, carbidopa and 5-hydroxytryptophan. One patient with partial PTPS deficiency was untreated and its growth and intelligence development were close to normal. Conclusion All patients with hyperphenylalaninemia must be screened for BH4 deficiency to reduce the rate of misdiagnosis. BH4 deficiency should be treated with BH4 and neurotransmitter progenitor as soon as possible.