Metabolomic profiling in phenylketonuria: a systematic review of human studies
A total of 26 human studies analyzing metabolites in urine and blood met the inclusion criteria. In total, 544 metabolites that differed between patients with PKU and healthy controls were identified through different metabolomic techniques (LC-MS, GC-MS, NMR). Differences were primarily observed in blood samples, which accounted for 95% of the total metabolites, with only 5% detected in urine samples, reflecting the limited use of this body fluid in only five studies. We found 60% of blood metabolites upregulated in patients with PKU, including Phe, Phe-related metabolites, lipids, and other amino acids, while tryptophan and kynurenine, among others, were downregulated (40%). Additionally, 35 metabolites (6% of the total) exhibited inconsistent directions of change (both up- and downregulated), including amino acids, carnitine derivatives, and lipids. These findings may be attributed to clinical factors (dietary adherence, supplementation, and treatment) and methodological differences in blood-derived matrices. Consequently, the high heterogeneity across studies, biological matrices and analytical platforms represents limitations for establishing a unique metabolomic signature. Overall, these results emphasize the metabolic complexity of PKU and highlight the potential of metabolomics to advance disease monitoring and management.
Authors
- Mireia Urpí-Sardà (ORCID: https://orcid.org/0000-0002-4064-5175)
- Dolores García-Arenas (ORCID: https://orcid.org/0000-0001-7487-0250)
- Carme Junqué (ORCID: https://orcid.org/0000-0002-6381-3063)
- Rafael Llorach
- P. Moreno (ORCID: https://orcid.org/0000-0002-2412-5460)
- Blanca Barrau-Martínez (ORCID: https://orcid.org/0000-0002-5700-5262)
- Francesc M. Campins-Machado (ORCID: https://orcid.org/0009-0006-2162-1756)
- Adriana Pané
- Emilio Ortega
- Aida Ormazabal
- Hadia Bakkali-Aissaoui
- Gloria Garrabou
- Arnau Gonzalez-Rodriguez
- Judit Garcia-Villoria
Institutions
- Hospital Sant Joan de Déu Barcelona (ES)
- Instituto de Salud Carlos III (ES)
- Departament de Salut (ES)
- Hospital Clínic de Barcelona (ES)
- Institut d'Investigacions Biomèdiques de Barcelona (ES)
- Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (ES)
- Fundació Clínic per a la Recerca Biomèdica (ES)
- Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES)
- Instituto de Investigación de Enfermedades Raras (ES)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Metabolomics
- Published
- 2026-03-07
- DOI
- https://doi.org/10.1007/s11306-026-02416-6
- Primary Topic
- Metabolism and Genetic Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Indian National Science Academy
- Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable
- Generalitat de Catalunya
- Universitat de Barcelona
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
- Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
- Agència de Gestió d'Ajuts Universitaris i de Recerca
- Instituto de Salud Carlos III
- European Regional Development Fund
- Agencia Estatal de Investigación