Dataset Information

Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria.

ABSTRACT:

Background

Several studies have highlighted disturbance of redox homeostasis in patients with phenylketonuria (PKU) which may be associated with neurological disorders observed in patients, especially during adulthood when phenylalanine restrictive diets are not maintained. The aim of this study was to assess the antioxidant profile in a cohort of PKU patients in comparison to the controls and to evaluate its relation to biochemical parameters especially phenylalaninemia.

Methods

We measured RNA expression of 22 antioxidant genes and reactive oxygen species (ROS) levels in white blood cells of 10 PKU patients and 10 age- and gender-matched controls. We also assessed plasma amino acids, vitamins, oligo-elements, and urinary organic acids concentrations. Then we evaluated the relationship between redox status and biochemical parameters.

Results

In addition to expected biochemical disturbances, we highlighted a significant global decrease of antioxidant genes expression in PKU patients in comparison to the controls. This global decrease of antioxidant genes expression, including various isoforms of peroxiredoxins, glutaredoxins, glutathione peroxidases, and superoxide dismutases, was significantly correlated to hyperphenylalaninemia.

Conclusion

This study is the first to evaluate the expression of 22 antioxidant genes in white blood cells regarding biochemical parameters in PKU. These findings highlight the association of hyperphenylalaninemia with antioxidant genes expression. New experiments to specify the role of oxidative stress in PKU pathogenesis may be useful in suggesting new recommendations in PKU management and new therapeutic trials based on antioxidant defenses.

SUBMITTER: Veyrat-Durebex C

PROVIDER: S-EPMC5740050 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria.

Veyrat-Durebex Charlotte C Debeissat Christelle C Blasco Hélène H Patin Franck F Henique Hélène H Emond Patrick P Antar Catherine C Gissot Valérie V Herault Olivier O Maillot François F

JIMD reports 20170315

<h4>Background</h4>Several studies have highlighted disturbance of redox homeostasis in patients with phenylketonuria (PKU) which may be associated with neurological disorders observed in patients, especially during adulthood when phenylalanine restrictive diets are not maintained. The aim of this study was to assess the antioxidant profile in a cohort of PKU patients in comparison to the controls and to evaluate its relation to biochemical parameters especially phenylalaninemia.<h4>Methods</h4> ...[more]

PMID: 28293905

Similar Datasets

Project description:BackgroundPhenylketonuria (PKU) represents a congenital metabolic defect that disrupts the process of converting phenylalanine (Phe) into tyrosine. Earlier investigations have revealed diminished cognitive performance and changes in brain structure and function (including the presence of white matter lesions) among individuals affected by PKU. However, there exists limited understanding regarding cerebral blood flow (CBF) and its potential associations with cognition, white matter lesions, and metabolic parameters in patients with PKU, which we therefore aimed to investigate in this study.MethodArterial spin labeling perfusion MRI was performed to measure CBF in 30 adults with early-treated classical PKU (median age 35.5 years) and 59 healthy controls (median age 30.0 years). For all participants, brain Phe levels were measured with 1H spectroscopy, and white matter lesions were rated by two neuroradiologists on T2 weighted images. White matter integrity was examined with diffusion tensor imaging (DTI). For patients only, concurrent plasma Phe levels were assessed after an overnight fasting period. Furthermore, past Phe levels were collected to estimate historical metabolic control. On the day of the MRI, each participant underwent a cognitive assessment measuring IQ and performance in executive functions, attention, and processing speed.ResultsNo significant group difference was observed in global CBF between patients and controls (F (1, 87) = 3.81, p = 0.054). Investigating CBF on the level of cerebral arterial territories, reduced CBF was observed in the left middle and posterior cerebral artery (MCA and PCA), with the most prominent reduction of CBF in the anterior subdivision of the MCA (F (1, 87) = 6.15, p = 0.015, surviving FDR correction). White matter lesions in patients were associated with cerebral blood flow reduction in the affected structure. Particularly, patients with lesions in the occipital lobe showed significant CBF reductions in the left PCA (U = 352, p = 0.013, surviving FDR correction). Additionally, axial diffusivity measured with DTI was positively associated with CBF in the ACA and PCA (surviving FDR correction). Cerebral blood flow did not correlate with cognitive performance or metabolic parameters.ConclusionThe relationship between cerebral blood flow and white matter indicates a complex interplay between vascular health and white matter alterations in patients with PKU. It highlights the importance of considering a multifactorial model when investigating the impact of PKU on the brain.

Dataset Information

Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria.

Background

Methods

Results

Conclusion

Publications

Hyperphenylalaninemia Correlated with Global Decrease of Antioxidant Genes Expression in White Blood Cells of Adult Patients with Phenylketonuria.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets