Abstract: 【Object】 To discuss the classification and treatment effect evaluation and genetic analysis of hyperphenylalaninemia(HPA) in Shandong. 【Mthods】 396 cases of HPA diagnosed by newborn screening in Jinan Classified according to BH4 loading test and urine pterin analysis.Different treatments were given and mornitor the concentration of Phe.The treatment effect was evaluated by the body development and mental development. 【Result】 Among 396 cases of HPA, 356 of them were PAHD,40 cases of BH4D,128 cases of BH4 responsed PAHD.There was no statistically significant difference between the different types of HPA patients and normal children by the body development,including weight and height.132 cases of HPA patients had normal mental development among 155 HPA.IQ of classical PKU( PAHD) showed negative correlation with the concentration of phe.IQ of BH4D patients corresponded with the diagnosed time.There were 6 gene mutation among 11 BH4D patients.42.1% of them were 259C>T. 【Conclusions】 The different clinic and biochemical HPA patients have no statistically significant difference for the body development after treatment while they have statistically significant difference for the intelligence development.The intelligence development level for Classical PKU corresponded with the concentration of Phe while that for BH4D corresponded with the diagnosed time.259C>T is the most common mutation of BH4D.

Key words: hyperphenylalaninemia, phenylalanine hydroxylase deficiency, etrahydrobiopterin deficiency

摘要： 【目的】 了解本省高苯丙氨酸血症(hyperphenylalaninemia,HPA)的分型、不同类型治疗效果、影响因素及四氢生物蝶呤缺乏症(tetrahydrobiopterin deficiency,BH4D)基因分析情况。 【方法】 对在济南市新生儿疾病筛查中心确诊的396例HPA患儿根据BH4负荷试验及尿蝶呤谱分析结果判断患儿的临床分型(苯丙氨酸羟化酶缺乏症及BH4D)。根据不同类型对症治疗,并定期监测血苯丙氨酸浓度及生长发育评价,对BH4D患儿进行基因分析。 【结果】396例HPA患儿中356例为苯丙氨酸羟化酶缺乏,40例BH4D,128例BH4反应性苯丙氨酸羟化酶缺乏症。155例随访患儿,末次随访6月~15岁,平均年龄6.5岁。治疗后HPA患儿体格发育与同年龄组正常儿童相比差异无统计学意义。155例HPA患儿智商正常132例(占85.2%)。经典型PKU患儿智商与血Phe浓度相关分析显示二者呈负相关(r=0.416,P<0.01)。BH4D患儿智商水平与开始治疗时有无神经系统症状密切相关。11例BH4D携带6种基因突变,259C>T占42.1%。 【结论】 不同临床表型和生化表型的HPA患儿经早期诊断治疗体格发均在正常范围,85%的患儿智力正常。经典型PKU患儿智力发育水平与血Phe浓度负相关,浓度的升高或波动较大均能严重影响患儿智力水平。BH4D患儿治疗效果与开始治疗的时间密切相关。本地区BH4D患儿较为集中的基因突变位点是259C>T。

关键词: 高苯丙氨酸血症, 苯丙氨酸羟化酶缺乏症, 四氢生物蝶呤缺乏症