目的 了解石家庄市新生儿高苯丙氨酸血症（HPA）的发病率、临床分型以及相关基因的变异特征。方法 选择2017年3月至2021年5月在石家庄市新生儿疾病筛查中心进行HPA筛查的487 380名新生儿，经免疫荧光法检测其足跟血苯丙氨酸浓度，采用基因测序技术对可疑阳性患儿苯丙氨酸羟化酶（PAH）基因进行检测，患儿父母采用Sanger法进行目标基因变异验证，进一步将基因测序结果与正常人比对，找出片段缺失区域并进行分析。结果 487 380名新生儿中筛查出阳性儿191例，确诊HPA 104例，均为PAH缺乏症，发病率为1/4686。104例患儿中共检测出62种基因变异，包括错义变异37种、剪接变异10种、无义变异7种、同义变异2种、整码变异1种以及杂合缺失5种。PAH基因常见的变异位点有c.158G>A（18.7%）、c.728G>A（10.5%）、c.611A>G（6.7%）、c.331C>T（4.8%）和c.721C>T（4.8%），并发现未报道基因片段缺失（外显子6杂合缺失）及基因变异（c.630T>G、c.61-1G>A、c.912+5G>T和c.1055+241C>A）。结论 石家庄市HPA发病率较高，为1/4686;发现了62种PAH基因变异，包括5种片段缺失;此外发现5种未报道的基因变异，丰富了基因数据库。

Objective To understand the incidence, clinical typing, and variant characteristics of related genes in neonates with hyperphenylalaninemia (HPA) in Shijiazhuang. Methods 487,380 newborns underwent HPA screening in Shijiazhuang Disease Screening and Diagnosis Center from March 2017 to May 2021 were selected. The phenylalanine concentration in heel blood samples was detected by immunofluorescence, the phenylalanine hydroxylase (PAH) related genes of suspected positive children were detected by gene sequencing, and the target gene variants were verified by the Sanger sequencing in the parents of the children, and the results of gene sequencing were further compared with the normal people to fragment deletion regions. Results Among the 487,380 neonates, 191 were screened positive and 104 were diagnosed as HPA, all with PAH deficiency, with a prevalence of 1/4686. A total of 62 genetic variations were detected in 104 children, including 37 missense mutations, 10 splice mutations, 7 nonsense mutations, 2 synonymous mutations, 1 full code mutation and 5 heterozygous deletions. The most common variants of PAH gene are c.158G>A (18.7%), c.728G>A (10.5%), c.611A>G (6.7%), c.331C>T (4.8%) and c.721C>T (4.8%), and unreported gene fragment deletions (exon 6 heterozygous deletion) and gene variants (c.630T>G, c.61-1G>A, c.912+5G>A) were found. Conclusions The prevalence of HPA in Shijiazhuang was high at 1/4686; 62 PAH gene variants, including 5 fragment deletions, were identified; in addition, 5 unreported gene variants were found, which enriches the gene database.