|
KMID : 0918520170170010011
|
|
Journal of the Korean Society of Inherited Metabolic Disease
2017 Volume.17 No. 1 p.11 ~ p.17
|
|
|
Ten Cases of R53H Variant of PAH Gene in Benign Hyperphenylalaninemia
|
|
Lee Ji-Yun
Lee Jeong-Ho
Lee Dong-Hwan
|
|
|
Abstract
|
|
|
Purpose: Phenylketonuria (PKU) results from a deficiency of phenylalanine hydroxylase (PAH). The mutation of the PAH gene results in decreased phenylalanine hydroxylase enzyme activity in hyperphenylalaninemia (HPA) patients. This study reports ten cases of patients with the benign HPA genotype c.158G>A (p.Arg53His, R53H) variant in the PAH gene and aims to evaluate the clinical significance of the R53H variant.
Methods: Ten Korean patients with the HPA genotype the R53H variant were included in this study. A retrospective medical record review was conducted. We characterized the phenotypes of the patients with HPA with the R53H variant using the following system: classic PKU, moderate PKU, mild PKU, Mild HPA, and benign HPA.
Results: Five patients had the R53H variant with the “Pathogenic” variants (R413P, R241C, Y356*, c.442-1G>A, Y325*), Two patients had the “Likely pathogenic” variants (W187*, A259T), Two patients had the “Uncertain significance” variants (R53H, G344D), and One patient had the “Not provided” variant (c.1066-14C>G). Nine patients genotyped with the R53H variant were the patient with benign HPA and One patient genotyped with the R53H homozygote was within normal range of plasma phenylalanine. None of the ten patients required dietary restriction of phenylalanine or pharmacotherapy to maintain their plasma phenylalanine levels and showed no clinical symptoms of HPA.
Conclusion: Ten patients with HPA genotype the R53H variant were the patient with benign HPA and showed no clinical symptoms of HPA. Thus, the R53H variant, which was previously classified as an “Uncertain significance” mutation in HPA patients, should be re-classified as “Benign.”
|
|
|
KEYWORD
|
|
|
Phenylketonuria, Hyperphenylalaninemia, Phenylalanine, PAH
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|