Abstract
Phenylketonuria (PKU) is a disease of the catabolism of phenylalanine (Phe), caused by an impaired function of the enzyme phenylalanine hydroxylase. Therapeutics is based on the restriction of Phe intake, which mostly requires a modification of the diet. Dietary restrictions can lead to imbalances in specific nutrients, including lipids. In the present study, the plasma phospholipidome of PKU and healthy children (CT) was analyzed by hydrophilic interaction liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry. Using this approach, 187 lipid species belonging to nine different phospholipid classes and three ceramides were identified. Principal component analysis of the lipid species data set showed a distinction between PKU and CT groups. Univariate analysis revealed that 146 species of phospholipids were significantly different between both groups. Lipid species showing significant variation included phosphatidylcholines, containing polyunsaturated fatty acids (PUFA), which were more abundant in PKU. The high level of PUFA-containing lipid species in children with PKU may be related to a diet supplemented with PUFA. This study was the first report comparing the plasma polar lipidome of PKU and healthy children, highlighting that the phospholipidome of PKU children is significantly altered compared to CT. However, further studies with larger cohorts are needed to clarify whether these changes are specific to phenylketonuric children.
Highlights
Phenylketonuria (PKU) is the most prevalent inborn error in amino acid metabolism 1–3
Our study reports a significant increase of 6 SM in the plasma of PKU children, compared to the CT group
The present study reports, for the first time, the application of mass spectrometry-based lipidomics to identify the plasma phospholipidome of children with phenylketonuria and healthy children
Summary
Phenylketonuria (PKU) is the most prevalent inborn error in amino acid metabolism 1–3. PKU is characterized by an impaired activity of the enzyme phenylalanine hydroxylase (PAH), resulting in a complete or partial inability of the enzyme to convert L-phenylalanine (Phe) to L-tyrosine. Deficiency of the PAH enzyme results in increased levels of P he in the blood (hyperphenylalaninemia) 4–6. The accumulation of Phe can lead to intellectual impairment, microcephaly, seizures, and motor deficits 2,7,8. Diagnosis through neonatal screening and rapid therapeutic implementation are essential to prevent these possible complications 9. The therapeutic approach for PKU is based on a lifelong Pherestricted diet, with a low intake of natural proteins 1
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have