2024/11/27 by Raphaela Muri, Murray Bruce Reed, Stephanie Maissen‐Abgottspon +5 · 1 voice
Medicine · Biochemistry, Genetics and Molecular Biology · #Advanced Neuroimaging Techniques and Applications #Metabolism and Genetic Disorders #Advanced MRI Techniques and Applications
paper · pdf · doi:10.1002/jimd.12823
openalex publication_date 2024/11/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28
Alterations in brain structure are frequently observed in adults with early-treated phenylketonuria (PKU) compared to healthy controls, with cerebral white matter (WM) being particularly affected. The extent to which temporary elevation of phenylalanine (Phe) levels impacts WM remains unclear. We conducted a double-blind, randomised, placebo-controlled crossover trial to investigate the effects of a 4-week high Phe exposure on cerebral WM and its relationship to cognitive performance and metabolic parameters in adults with PKU. In this study, 27 adults with early-treated classical PKU (aged 19-48 years) underwent diffusion tensor imaging (DTI) before and after the 4-week Phe and placebo interventions. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were analysed using tract-based spatial statistics. Neuropsychological examinations at each timepoint evaluated executive functions and attention. Additionally, brain Phe levels were measured using MR spectroscopy, and blood levels of Phe, tyrosine, and tryptophan were assessed after an overnight fast. Following the Phe period, significant decreases in AD, MD, and RD were observed compared to the placebo period, particularly in the posterior corona radiata and optic radiation. Notably, these WM changes were reversible in patients who first received Phe (n = 13). Cognitive performance and metabolic parameters were not significantly related to DTI scalars after the Phe period. In conlcusion, a 4-week Phe elevation induced reversible microstructural alterations in cerebral WM. Further investigation is necessary to determine the clinical implication of these changes.