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Article

Clinical and Genetic Characteristics of Patients with Mild Hyperphenylalaninemia Identified by Newborn Screening Program in Japan

1
Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
2
Department of Medical Statistics, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
3
Department of Biostatistics, Yokohama City University School of Medicine, Yokohama 236-0004, Japan
4
Donated Course “Disability Medicine and Regenerative Medicine”, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
*
Author to whom correspondence should be addressed.
Int. J. Neonatal Screen. 2021, 7(1), 17; https://0-doi-org.brum.beds.ac.uk/10.3390/ijns7010017
Received: 23 February 2021 / Revised: 13 March 2021 / Accepted: 15 March 2021 / Published: 18 March 2021
(This article belongs to the Collection 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 μmol (95% CI 152.088–172.343) at 50–60 months of age and did not exceed 360 μmol/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. View Full-Text
Keywords: phenylketonuria; hyperphenylalaninemia; phenylalanine hydroxylase; genetic analysis; neonatal screening; genotype–phenotype correlation phenylketonuria; hyperphenylalaninemia; phenylalanine hydroxylase; genetic analysis; neonatal screening; genotype–phenotype correlation
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MDPI and ACS Style

Odagiri, S.; Kabata, D.; Tomita, S.; Kudo, S.; Sakaguchi, T.; Nakano, N.; Yamamoto, K.; Shintaku, H.; Hamazaki, T. Clinical and Genetic Characteristics of Patients with Mild Hyperphenylalaninemia Identified by Newborn Screening Program in Japan. Int. J. Neonatal Screen. 2021, 7, 17. https://0-doi-org.brum.beds.ac.uk/10.3390/ijns7010017

AMA Style

Odagiri S, Kabata D, Tomita S, Kudo S, Sakaguchi T, Nakano N, Yamamoto K, Shintaku H, Hamazaki T. Clinical and Genetic Characteristics of Patients with Mild Hyperphenylalaninemia Identified by Newborn Screening Program in Japan. International Journal of Neonatal Screening. 2021; 7(1):17. https://0-doi-org.brum.beds.ac.uk/10.3390/ijns7010017

Chicago/Turabian Style

Odagiri, Shino, Daijiro Kabata, Shogo Tomita, Satoshi Kudo, Tomoko Sakaguchi, Noriko Nakano, Kouji Yamamoto, Haruo Shintaku, and Takashi Hamazaki. 2021. "Clinical and Genetic Characteristics of Patients with Mild Hyperphenylalaninemia Identified by Newborn Screening Program in Japan" International Journal of Neonatal Screening 7, no. 1: 17. https://0-doi-org.brum.beds.ac.uk/10.3390/ijns7010017

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