Abstract: 　Objective　To explore the PAH gene variation spectrum of phenylalanine hydroxylase (PAH) deficiency in children, and to explore the relationship between genotype and phenotype. Method　The PAH gene mutation sites in 76 children with PAH deficiency confirmed by neonatal screening were analyzed retrospectively, and the genotype-phenotype prediction model was established. Alleles were assigned, specific values of mutation sites (AV) were set, and the sum of AV scores was calculated to predict the clinical phenotype. Results　Using the second-generation high-throughput sequencing technology and multiplex ligation-dependent probe amplification technology, 146 mutation sites were detected in 152 PAH alleles in 76 neonates and the frequency was 96.1%. Two variant alleles were detected in 70 newborns, including 3 homozygous and 67 compound heterozygous variants. One variant allele was detected in the other 6 newborns. A total of 45 types of variation were detected, and the locus with high frequency of variation was c.728G>A (26/146, 17.8%), c.158G>A (13/146, 8.9%), and c.1068C>A ( 11/146, 7.5%), c.721C>T (10/146, 6.8%), c.1238G>C (8/146, 5.5%), c.331C>T (8/146, 5.5%) and c.1301C>A (7/146, 4.8%). The c.95A>G locus has not been reported by BIOPKU database. There was a significantly negative correlation between serum phenylalanine (Phe) concentration and the sum of AV scores before treatment (r=－0.83, P<0.001). During follow-up, it was found that 2 mild hyperphenylalaninemia children whose blood Phe concentration was less than 120 μmol/ L did not require treatment. Conclusion　Constructing common PAH gene variation spectrum and verifying the correlation between PAH gene mutation and phenotype are conducive to diagnosis and typing of PAH, early prognosis judgment, and genetic counseling.

Key words: 　hyperphenylalaninemia;　phenylalanine hydroxylase;　genotype;　child