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

Claire Cannet, Allan Bayat, Georg Frauendienst-Egger, Peter Freisinger, Manfred Spraul, Nastassja Himmelreich, Musa Kockaya, Kirsten Ahring, Markus Godejohann, Anita MacDonald, Friedrich Trefz*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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 (1H-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.

Original languageEnglish
Article number4916
JournalMolecules
Volume28
Issue number13
Number of pages19
ISSN1420-3049
DOIs
Publication statusPublished - Jul 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

  • Ex Vivo 1H-NMR analysis spectroscopy
  • genotype
  • metabolomics
  • pathogenesis
  • phenylketonuria

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