目的 探讨青岛地区6-丙酮酰四氢蝶呤合成酶缺乏症（PTPSD）筛查情况、临床表现、基因变异情况及长期随访结果。方法 对1996年11月至2021年12月经新生儿筛查确诊的251例高苯丙氨酸血症（HPA）患儿进行尿蝶呤谱检测、红细胞二氢蝶呤还原酶活性检测、四氢生物蝶呤（BH4）负荷试验及基因检测以确诊PTPSD，进一步分析青岛市PTPSD的发生率、基因变异特点及长期随访结果。结果 251例HPA患儿中，26例诊断为四氢生物蝶呤缺乏症（2对单卵双胞胎、1对为非同胎生姐妹），均为PTPSD，发病率为12.7/100万（双胎按1例计算）。19例患儿（来自17个家庭）进行基因检测，PTPS的34个等位基因中共检测出10种变异，变异频率较高的为c.259C>T（29.4%，10/34），其余依次为c.286G>A（14.7%，5/34）、c.272A>G（14.7%，5/34）、c.84-291A>G（8.8%，3/34）、c.166G>A(8.8%，3/34)、c.276T>A (8.8%，3/34)，变异位点主要集中在5号外显子67.6%（23/34）。其中c.200C>T、c.259C>T、c.286G>A可能导致严重型PTPSD。结论 1996－2021年青岛地区PTPSD发生率为12.7/100万，PTPS基因的热点突变为c.259C>T、c.286G>A、c.272A>G。建立完善的新生儿疾病筛查-诊断-治疗-长期随访-救助的一体化管理体系是作好出生缺陷第三级预防，降低残疾儿发生的有力措施。

Objective To investigate the screening, clinical manifestations, genetic variants and long-term follow-up results of 6-pyruvoyltetrahydropterin synthase deficiency (PTPSD) in Qingdao. Methods Two hundred and fifty-one children with hyperphenylalaninemia (HPA) in Qingdao Women and Children's Hospital from November 1998 to December 2021 were included, and urinary pterin profile test, erythrocyte dihydropteroate reductase activity test, tetrahydrobiopterin (BH4) loading test, and genetic test were performed to confirm the diagnosis of PTPSD. The incidence, gene mutations and long-term follow-up of PTPSD were analyzed. Results Twenty-six children were diagnosed as tetrahydrobioptenin deficiency (BH4D), all PTPSD, and the incidence of PTPSD among newborns in Qingdao was 12.7 per million. 19 children (from 17 families) underwent genetic testing, and 10 variants were detected among 34 alleles of PTS, with the higher frequency of variants being c.259C>T (29.4%, 10/34), and the rest were c.286G>A (14.7%, 5/34), c.272A>G (14.7%, 5/34), c.84-291A>G (8.8%, 3/34), c.166G>A (8.8%, 3/34), c.276T>A (8.8%, 3/34 ), and the variant sites were mainly concentrated in exon 5 (67.6%, 23/34). Among them, c.200C>T, c.259C>T and c.286G>A may be associated with severe PTPSD. Conclusion The incidence of PTPSD in Qingdao is 12.7/ million in 1996-2021, and the hotspot variants of PTS gene are c.259C>T, c.286G>A, c.272A>G. Establishment of a complete integrated management system of newborn disease screening-diagnosis-treatment-long-term follow-up-assistance is a powerful measure to achieve a tertiary prevention of birth defects and reduce the occurrence of disabled children.