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Plasma metabolomic profile changes in females with phenylketonuria following a camp intervention.
- Source :
-
The American journal of clinical nutrition [Am J Clin Nutr] 2022 Mar 04; Vol. 115 (3), pp. 811-821. - Publication Year :
- 2022
-
Abstract
- Background: There remains a limited understanding of the metabolic perturbations, beyond phenylalanine (Phe) metabolism, that contribute to phenotypic variability in phenylketonuria (PKU).<br />Objectives: This study aimed to characterize changes in the PKU plasma metabolome following a 5-d metabolic camp intervention and to compare PKU profiles with those of matched healthy controls.<br />Methods: In 28 females (aged 12-57 y), fasting plasma samples were collected on the first (day 1) and final (day 5) days of camp to measure metabolic control and to complete untargeted metabolomic profiling. Three-day dietary records were collected to assess changes in dietary adherence and composition. Univariate (Wilcoxon signed-rank and Mann-Whitney U test) and multivariate (random forest, hierarchical clustering) analyses were performed to identify clinical and metabolic features that were associated with the intervention and disease state.<br />Results: Relative to healthy controls, Phe catabolites, ketones, and carnitine- and glycine-conjugated fatty acids were elevated in females with PKU at baseline, whereas fatty acylcholine metabolites were substantially lower. After the camp intervention, plasma Phe concentrations decreased [median change: -173 µmol/L (IQR: -325, -28 µmol/L)] and 70% of PKU participants demonstrated improved dietary adherence by decreasing Phe intake and/or increasing medical food consumption. This was accompanied by a shift in abundance for 223 metabolites (q < 0.05). Compounds associated with the metabolism of Phe, fatty acids, and choline contributed most to profile differences between camp days 1 and 5.<br />Conclusions: In females with PKU, untargeted metabolomics identified prominent perturbations in amino acid and lipid metabolites associated with bioenergetic impairment and oxidative stress. Choline-conjugated lipids could have fundamental roles in these pathways and they have not been previously evaluated in PKU. A short-term camp intervention was effective for improving or fully normalizing the abundance of the identified discriminatory metabolites.<br /> (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)
- Subjects :
- Carnitine
Choline
Fatty Acids
Female
Humans
Metabolomics
Phenylketonurias
Subjects
Details
- Language :
- English
- ISSN :
- 1938-3207
- Volume :
- 115
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The American journal of clinical nutrition
- Publication Type :
- Academic Journal
- Accession number :
- 34864852
- Full Text :
- https://doi.org/10.1093/ajcn/nqab400