北京地区PKU筛查、诊疗及基因分析

The PKU neonatal screening, diagnosis,treatment and genic mutational analysis in Beijing area

【目的】 对北京地区筛查确诊PKU患儿进行追踪诊疗和基因检测 ,了解该地区人群PKU患者基因突变种类和分布。 【方法】 对 1993～ 2 0 0 2年在京出生的新生儿进行PKU筛查 ,采用Guthrie细菌抑制法和毛细管电泳测定血苯丙氨酸浓度 ;对确诊的PKU患儿给予无苯丙氨酸奶粉追踪治疗 ;并应用多重等位基因特异PCR(MASPCR)等方法对 40例PKU家系进行了基因突变的检测。 【结果】 1993～ 2 0 0 2年经过新生儿筛查共确诊PKU 64例、HPA 14例、BH4缺乏症 4例 ,经随访治疗 86%患儿的智能发育达正常同龄儿水平。DQ >85的PKU患儿开始治疗平均年龄为生后 47d ,且配合治疗者占 79.1%;而DQ <85的患儿开始治疗平均年龄为生后 12 0d ,不配合治疗 86%。对 40例PKU家系进行基因检测 ,发现 8种突变占 5 1.2 5 %,其中Arg2 43Gln发生率最高、依次为Tyr2 0 4Cys、Tyr3 5 6Ter、Arg111Ter、Arg413Pro、Arg2 5 2Gln、Tyr161Ser、IVS4nt( 1) g >a。 【结论】 协调统一的组织管理和严格的质量控制是开展新生儿筛查的保证 ;PKU患儿需早期正规治疗 ,才能获得满意的治疗效果 ;

The clinical diagnosis ,treatment, and gene analysis of PKU patients were studied in Beijing area, to explore the gene mutation types and distributions. Neonatal PKU screening was performed at born among 1993～2002. The blood phenylalanine concentration was determined with Guthrie bacterial inhibition assay and capillary electrophoresis, PKU patients were treated with the free Phenylalanine formula , the PKU gene was detected for mutations in 40 PKU patients with multiplex allele specific PCR(MASPCR). 64 cases of phenylketonuria( PKU) had been confirmed after neonatal screening,14 cases of hyperphenylalaninemia(HPA), 4 cases of the tetrahydrobiopterin deficiency(BH 4D) had been confirmed. After follow up treatment, 87% of patients’intelligence developed as same as the healthy children. The average age of PKU patients (DQ>85) starting treatment was 47days after the birth. The starting age of patients (DQ<85) for treatment was 120 days after birth. No cooperation with treatment were 86%. The result of the gene detection for the 40 family cases, 8 mutations (51.25%) were found, the Arg243gln was the highest, The result of 204Cys, Tyr356Ter, Arg111Ter, Arg413Pro, Arg252Gln, Tyr161Ser, IVS4nt( 1)g >a.[Conclusions] The correspond management and strict quality control are the guarantee for the neonatal screening development; the PKU patients need the early and regular treatment, and gain the satisfactory treatment result. The gene detection and analysis are very necessary for prenatal diagnosis of PKU.