期刊
INTERNATIONAL JOURNAL OF NEONATAL SCREENING
卷 7, 期 1, 页码 -出版社
MDPI
DOI: 10.3390/ijns7010017
关键词
phenylketonuria; hyperphenylalaninemia; phenylalanine hydroxylase; genetic analysis; neonatal screening; genotype-phenotype correlation
资金
- Health and Labor Sciences Research Grant [20316977]
- AMED [JP16ek0109050, JP19ek0109276, JP20ek0109482]
Phenylketonuria (PKU) and hyperphenylalaninemia (HPA) are caused by variants in the PAH gene. The p.R53H variant is common in HPA patients in East Asia. Patients with HPA carrying the p.R53H variant do not require frequent Phe monitoring and the study provides evidence for clinical management of patients detected through newborn screening in Japan.
Phenylketonuria (PKU) and hyperphenylalaninemia (HPA), both identified in newborn screening, are attributable to variants in PAH. Reportedly, the p.R53H(c.158G>A) variant is common in patients with HPA in East Asia. Here, we aimed to define the association between p.R53H and HPA phenotype, and study the long-term outcome of patients with HPA carrying p.R53H. We retrospectively reviewed the genotype in 370 patients detected by newborn screening, and identified the phenotype in 280 (117, HPA; 163, PKU). p.R413P(c.1238G>C) was the most frequently found (n = 117, 31.6%) variant, followed by p.R53H (n = 89, 24.1%). The odds ratio for heterozygous p.R53H to cause HPA was 48.3 (95% CI 19.410-120.004). Furthermore, we assessed the non-linear association between the phenylalanine (Phe) value and elapsed time using the follow-up data of the blood Phe levels of 73 patients with HPA carrying p.R53H. The predicted levels peaked at 161.9 mu mol (95% CI 152.088-172.343) at 50-60 months of age and did not exceed 360 mu mol/L during the 210-month long observation period. The findings suggest that patients with HPA, carrying p.R53H, do not need frequent Phe monitoring as against those with PKU. Our study provides convincing evidence to determine clinical management of patients detected through newborn screening in Japan.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据