{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:44:58Z","timestamp":1790628298018,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,22]],"date-time":"2023-06-22T00:00:00Z","timestamp":1687392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 \u00b1 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 &lt; 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.<\/jats:p>","DOI":"10.3390\/molecules28134916","type":"journal-article","created":{"date-parts":[[2023,6,23]],"date-time":"2023-06-23T02:34:07Z","timestamp":1687487647000},"page":"4916","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Phenylketonuria (PKU) Urinary Metabolomic Phenotype Is Defined by Genotype and Metabolite Imbalance: Results in 51 Early Treated Patients Using Ex Vivo 1H-NMR Analysis"],"prefix":"10.3390","volume":"28","author":[{"given":"Claire","family":"Cannet","sequence":"first","affiliation":[{"name":"Bruker Biospin, 76275 Ettlingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4986-8006","authenticated-orcid":false,"given":"Allan","family":"Bayat","sequence":"additional","affiliation":[{"name":"Kennedy Centre, Center for PKU, 2600 Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Frauendienst-Egger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Freisinger","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, University of T\u00fcbingen, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Spraul","sequence":"additional","affiliation":[{"name":"Bruker Biospin, 76275 Ettlingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nastassja","family":"Himmelreich","sequence":"additional","affiliation":[{"name":"CEGAT, Human Genetic Institute, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Musa","family":"Kockaya","sequence":"additional","affiliation":[{"name":"Private Pediatric Practice, 68307 Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Ahring","sequence":"additional","affiliation":[{"name":"Kennedy Centre, Center for PKU, 2600 Glostrup, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9702-7802","authenticated-orcid":false,"given":"Markus","family":"Godejohann","sequence":"additional","affiliation":[{"name":"Bruker Biospin, 76275 Ettlingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Dietetic Department, Birmingham Children\u2019s Hospital, Birmingham B4 6NH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7706-7463","authenticated-orcid":false,"given":"Friedrich","family":"Trefz","sequence":"additional","affiliation":[{"name":"Metabolic Consulting Reutlingen, 72766 Reutlingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s13023-017-0685-2","article-title":"The complete European guidelines on phenylketonuria: Diagnosis and treatment","volume":"12","author":"MacDonald","year":"2017","journal-title":"Orphanet J. 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