Plasma metabolomic profile changes in females with phenylketonuria following a camp intervention.

Abstract

BACKGROUND:

There remains a limited understanding of the metabolic perturbations, beyond phenylalanine (Phe) metabolism, that contribute to phenotypic variability in phenylketonuria (PKU).

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.

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.

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.

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.

• Authors: Meriah S Schoen, Rani H Singh
• Journal: The American journal of clinical nutrition (Am J Clin Nutr) Vol. 115 Issue 3 Pg. 811-821 (03 04 2022) ISSN: 1938-3207 [Electronic] United States
• PMID: 34864852 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.

Chemical References

• Fatty Acids
• Choline
• Carnitine

Topics

• Carnitine
• Choline
• Fatty Acids
• Female
• Humans
• Male
• Metabolomics
• Phenylketonurias