TY - JOUR
T1 - Impact of Phenylketonuria on the Serum Metabolome and Plasma Lipidome
T2 - A Study in Early-Treated Patients
AU - Weerd, Jorine C.van der
AU - Wegberg, Annemiek M.J.van
AU - Boer, Theo S.
AU - Engelke, Udo F.H.
AU - Coene, Karlien L.M.
AU - Wevers, Ron A.
AU - Bakker, Stephan J.L.
AU - Blaauw, Pim de
AU - Groen, Joost
AU - Spronsen, Francjan J.van
AU - Heiner-Fokkema, M. Rebecca
N1 - Publisher Copyright:
© 2024 by the authors.
PY - 2024/9
Y1 - 2024/9
N2 - Background: Data suggest that metabolites, other than blood phenylalanine (Phe), better and independently predict clinical outcomes in patients with phenylketonuria (PKU). Methods: To find new biomarkers, we compared the results of untargeted lipidomics and metabolomics in treated adult PKU patients to those of matched controls. Samples (lipidomics in EDTA-plasma (22 PKU and 22 controls) and metabolomics in serum (35 PKU and 20 controls)) were analyzed using ultra-high-performance liquid chromatography and high-resolution mass spectrometry. Data were subjected to multivariate (PCA, OPLS-DA) and univariate (Mann–Whitney U test, p < 0.05) analyses. Results: Levels of 33 (of 20,443) lipid features and 56 (of 5885) metabolite features differed statistically between PKU patients and controls. For lipidomics, findings include higher glycerolipids, glycerophospholipids, and sphingolipids species. Significantly lower values were found for sterols and glycerophospholipids species. Seven features had unknown identities. Total triglyceride content was higher. Higher Phe and Phe catabolites, tryptophan derivatives, pantothenic acid, and dipeptides were observed for metabolomics. Ornithine levels were lower. Twenty-six metabolite features were not annotated. Conclusions: This study provides insight into the metabolic phenotype of PKU patients. Additional studies are required to establish whether the observed changes result from PKU itself, diet, and/or an unknown reason.
AB - Background: Data suggest that metabolites, other than blood phenylalanine (Phe), better and independently predict clinical outcomes in patients with phenylketonuria (PKU). Methods: To find new biomarkers, we compared the results of untargeted lipidomics and metabolomics in treated adult PKU patients to those of matched controls. Samples (lipidomics in EDTA-plasma (22 PKU and 22 controls) and metabolomics in serum (35 PKU and 20 controls)) were analyzed using ultra-high-performance liquid chromatography and high-resolution mass spectrometry. Data were subjected to multivariate (PCA, OPLS-DA) and univariate (Mann–Whitney U test, p < 0.05) analyses. Results: Levels of 33 (of 20,443) lipid features and 56 (of 5885) metabolite features differed statistically between PKU patients and controls. For lipidomics, findings include higher glycerolipids, glycerophospholipids, and sphingolipids species. Significantly lower values were found for sterols and glycerophospholipids species. Seven features had unknown identities. Total triglyceride content was higher. Higher Phe and Phe catabolites, tryptophan derivatives, pantothenic acid, and dipeptides were observed for metabolomics. Ornithine levels were lower. Twenty-six metabolite features were not annotated. Conclusions: This study provides insight into the metabolic phenotype of PKU patients. Additional studies are required to establish whether the observed changes result from PKU itself, diet, and/or an unknown reason.
KW - lipidomics
KW - mass-spectrometry
KW - metabolomics
KW - phenylalanine
KW - phenylketonuria
KW - untargeted
UR - http://www.scopus.com/inward/record.url?scp=85205259491&partnerID=8YFLogxK
U2 - 10.3390/metabo14090479
DO - 10.3390/metabo14090479
M3 - Article
AN - SCOPUS:85205259491
SN - 2218-1989
VL - 14
JO - Metabolites
JF - Metabolites
IS - 9
M1 - 479
ER -