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目的:探讨徐州地区新生儿苯丙酮尿症（phenylketonuria，PKU）筛查特征及构建徐州地区苯丙氨酸羟化酶（phenylalanine hydroxylase，PAH）基因和四氢生物蝶呤缺乏症相关基因突变谱。方法:选择2015年11月至2020年3月徐州地区出生并采用串联质谱技术进行苯丙氨酸（Phe）及苯丙氨酸与酪氨酸比值（Phe/Tyr）测定的新生儿资料进行回顾性研究，应用高通量测序联合Sanger测序技术对苯丙氨酸异常患儿进行基因分析。结果:共计完成450 355名新生儿苯丙氨酸相关指标测定，确诊115例PKU，患儿Phe及Phe/Tyr比值显著升高，PKU发病率为1∶3 916。其中PAH基因突变113例，PTS基因突变2例。PAH基因突变患儿中纯合子突变5例，PAH合并PTS双基因突变1例，PAH基因3位点突变2例。PAH基因高频突变类型为2号外显子错义突变，常见基因突变主要包括c.158G>A （p.R53H） （24.7％，56/227）、c.728G>A （p.R243Q） （15.0％，34/227）、c.611A>G （p.Y204C） （5.3％，12/227） 、c.721C>T （p.R241C） （5.3%，12/227）和c.1068C>A （p.Y356X） （4.8％，11/227）。共发现3个新的PAH基因突变（c.234dupA、c.441+15C>G和c.1096C>T）及1个新的PTS基因突变（c.286G>A）。结论:徐州地区PKU较常见，属于PKU高发地区，基因突变以PAH基因突变为主。“,”Objective:To study the characteristics of phenylketonuria (PKU) using tandem mass spectrometry for neonatal screening and the characteristics of genetic mutation spectrums of phenylalanine hydroxylase (PAH) deficiency and pyruvoyl-tetrahydropterin synthase (PTS) deficiency in Xuzhou area.Method:From November 2015 to March 2020, the phenylalanine (Phe) level and the ratio of phenylalanine to tyrosine (Phe/Tyr) were examined using tandem mass spectrometry. The infants with abnormal Phe level and Phe/Tyr ratio were further analyzed using high-throughput sequencing combined with Sanger sequencing.Result:450 355 neonates were enrolled. Phe levels and Phe/Tyr ratios were increased in 115 neonates. The incidence of PKU was 1∶3 916. 113 cases showed PAH gene mutation and 2 cases PTS gene mutation. Common genetic variations of PAH gene included c.158G>A (p.R53H) (24.7%, 56/227), c.728G>A (p.R243Q) (15.0%, 34/227), c.611A>G (p.Y204C) (5.3%, 12/227), c.721C>T (p.R241C) (5.3%, 12/227) and c.1068C>A (p.Y356X) (4.8%, 11/227). R53H was located on Exon2. In addition, 3 novel variants of PAH gene including c.234dupA, c.441+15C>G and c.1096C>T and 1 novel variant of PTS gene c.286G>A were identified.Conclusion:PKU is relatively common in Xuzhou area with a high incidence. The variants were mainly located on PAH gene.