Plasma metabolomic profile changes in females with phenylketonuria following a camp intervention.
Am J Clin Nutr
; 115(3): 811-821, 2022 03 04.
Article
in En
| MEDLINE
| ID: mdl-34864852
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phenylketonurias
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Am J Clin Nutr
Year:
2022
Document type:
Article
Affiliation country:
United States