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【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。
【Objective】 To investigate the classification of hyperphenylalaninemia (HPA) in the province, different types of treatment, influencing factors and gene analysis of tetrahydrobiopterin deficiency (BH4D). 【Methods】 A total of 396 cases of HPA diagnosed in Jinan Newborns Disease Screening Center were divided into three groups according to the BH4 load test and the results of urinary pterin analysis to determine the clinical type (phenylalanine hydroxylase deficiency and BH4D ). According to different types of symptomatic treatment, and regular monitoring of blood phenylalanine concentration and growth evaluation, gene analysis of BH4D children. 【Results】 Among the 396 HPA children, 356 cases were phenylalanine hydroxylase deficiency, 40 cases of BH4D and 128 cases of BH4-reactive phenylalanine hydroxylase deficiency. 155 cases were followed up, the last follow-up of 6 months to 15 years old, with an average age of 6.5 years. There was no significant difference between the physical development of HPA children and normal children in the same age group after treatment. 155 cases of HPA children with normal IQ 132 cases (85.2%). The correlation between IQ and Phe concentration in children with classical PKU showed a negative correlation (r = 0.416, P <0.01). The IQ of children with BH4D is closely related to the presence or absence of neurological symptoms at the beginning of treatment. Eleven cases of BH4D carry 6 kinds of gene mutations, 259C> T accounted for 42.1%. 【Conclusion】 HPA children with different clinical phenotypes and biochemical phenotypes are in the normal range after early diagnosis and treatment, and 85% of children have normal intelligence. The level of intellectual development in children with classical PKU was negatively correlated with the blood Phe concentration. The increase or fluctuation of the concentration of PKU could seriously affect the intelligence level of children. BH4D treatment of children with the onset of treatment is closely related to the time. The locus of BH4D in this area is 259C> T.