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Phenylketonuria (PKU) Urinary Metabolomic Phenotype Is Defined by Genotype and Metabolite Imbalance: Results in 51 Early Treated Patients Using Ex Vivo 1 H-NMR Analysis.

Authors :
Cannet, Claire
Bayat, Allan
Frauendienst-Egger, Georg
Freisinger, Peter
Spraul, Manfred
Himmelreich, Nastassja
Kockaya, Musa
Ahring, Kirsten
Godejohann, Markus
MacDonald, Anita
Trefz, Friedrich
Source :
Molecules; Jul2023, Vol. 28 Issue 13, p4916, 19p
Publication Year :
2023

Abstract

Phenylketonuria (PKU) is a rare metabolic disorder caused by mutations in the phenylalanine hydroxylase gene. Depending on the severity of the genetic mutation, medical treatment, and patient dietary management, elevated phenylalanine (Phe) may occur in blood and brain tissues. Research has recently shown that high Phe not only impacts the central nervous system, but also other organ systems (e.g., heart and microbiome). This study used ex vivo proton nuclear magnetic resonance (<superscript>1</superscript>H-NMR) analysis of urine samples from PKU patients (mean 14.9 ± 9.2 years, n = 51) to identify the impact of elevated blood Phe and PKU treatment on metabolic profiles. Our results found that 24 out of 98 urinary metabolites showed a significant difference (p < 0.05) for PKU patients compared to age-matched healthy controls (n = 51) based on an analysis of urinary metabolome. These altered urinary metabolites were related to Phe metabolism, dysbiosis, creatine synthesis or intake, the tricarboxylic acid (TCA) cycle, end products of nicotinamide-adenine dinucleotide degradation, and metabolites associated with a low Phe diet. There was an excellent correlation between the metabolome and genotype of PKU patients and healthy controls of 96.7% in a confusion matrix model. Metabolomic investigations may contribute to a better understanding of PKU pathophysiology. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14203049
Volume :
28
Issue :
13
Database :
Complementary Index
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
164920276
Full Text :
https://doi.org/10.3390/molecules28134916