Objective To investigate the incidence of neonatal hyperphenylalaninemia (HPA) and analyze the characteristics of HPA gene mutations in the Yangzhou area.

Methods From January 2013 to December 2022, 285, 549 newborns in Yangzhou were screened for HPA using either the ninhydrin fluorescence method or tandem mass spectrometry. Urinary pterin analysis, erythrocyte dihydrobiopterin reductase activity measurement and genetic diagnosis were performed to screen positive individuals.

Results A total of 29 cases were confirmed as HPA, including 3 cases of tetrahydrobiopterin (BH₄) deficiency and 26 cases of phenylalanine hydroxylase (PAH) deficiency. The overall incidence of HPA in Yangzhou was 1/9, 847, with the incidence of PAH deficiency being 1/10, 983, which were slightly higher than the national average but lower than other regions in Jiangsu Province. Among the cases, 13 (44.83%) were classic phenylketonuria (PKU), 7(24.14%) were mild PKU, and 6(20.69%) were mild HPA. Sixteen patients with PAH gene mutations were all compound heterozygotes, with one case exhibiting three-site mutations. PAH gene mutations were predominantly missense mutations, primarily concentrated in exon 7, followed by exon 6, with E7 c.728G>A (21.21%) being the most frequent mutation. Three cases of BH₄ deficiency were detected with PTS gene mutations, including 1 homozygous mutation and 2 compound heterozygous mutations. E5 c.259C>T was the high-frequency PTS mutation gene in Yangzhou.

Conclusion HPA has a certain incidence in Yangzhou, with classic PKU being the predominant type. This study clarified the characteristics of PAH and PTS gene mutations in Yangzhou, enriching the HPA gene database.