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目的了解我国各种病因所致的高苯丙氨酸血症(HPA)的发生率,探讨新生儿早期诊治患者血苯丙氨酸(Phe)控制与智能发育关系。方法对新生儿筛查发现的223例 HPA 患儿,采用四氢生物蝶呤(BH_4)负荷试验、尿蝶呤谱分析、二氢蝶啶还原酶活性测定进行病因诊断,对治疗者进行生长和智能发育评价,相关基因突变分析。结果 223例中苯丙氨酸羟化酶缺乏症(PAHD)129例(57.8%),BH_4反应性 PAHD 64例(28.7%),6-丙酮酰四氢蝶呤合成酶缺乏症(PTSD)30例(13.5%)。149例接受随访(年龄4个月至22岁),其中136例生后1.6个月(0.5～3.5个月)根据病因接受相应治疗,13例不需治疗随访。136例治疗者中108例(79.4%)智能发育正常,对58例患者进行智商(IQ)与血 Phe 浓度相关分析显示两者成负相关(r=-0.439,P<0.01)。9例 PTSD 者携带9种 PTS 基因突变,286G→A及259C→T占45%,13例 BH_4反应性 PAHD 者携带7种 PAH 基因突变,R241C 多见(43.8%)。结论新生儿筛查发现的 HPA 需快速进行病因鉴别诊断,早期治疗者近80%智能发育正常,血 Phe 浓度控制是智能发育的重要因素。
Objective To investigate the incidence of hyperphenylalaninemia (HPA) caused by various etiologies in China and to explore the relationship between the control of hemophilic phenylalanine (Phe) and the development of intelligence in the early diagnosis and treatment of neonates. Methods Totally 223 HPA infants who were diagnosed by neonatal screening were diagnosed etiologically by means of tetrahydrobiopterin (BH_4) stress test, urinary pterin flux spectrum and dihydropteridine reductase activity test, Evaluation of intelligent development, related gene mutation analysis. Results A total of 223 patients (57.8%) had phenylalanine hydroxylase deficiency (PAHD), 64 patients (28.7%) had BH4-responsive PAHD, and 30 had pyrethroid-synthesizing enzyme deficiency (PTSD) Example (13.5%). A total of 149 patients were followed up (range, 4 months to 22 years). 136 of them were treated for 1.6 months (0.5-3.5 months) according to their etiology. Thirteen patients were followed up without treatment. Of 136 patients, 108 (79.4%) had normal intelligence development. Correlation analysis between IQ and blood Phe concentrations in 58 patients showed a negative correlation (r = -0.439, P <0.01). Nine PTSD patients carried 9 PTS mutations, 286G → A and 259C → T accounted for 45%. 13 PAH patients with BH_4 reactive PAHD had 7 PAH mutations, and R241C was more common (43.8%). Conclusion HPA detected by neonatal screening should be used for the rapid diagnosis of etiology. Nearly 80% of early treatment patients have normal intelligence development and blood Phe concentration control is an important factor in the development of intelligence.