ArticleNeuroImage. Clinical2019
White and gray matter brain development in children and young adults with phenylketonuria.
Article in NeuroImage. Clinical, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Characterisation and differential diagnosis of neurological complications in adults with phenylketonuria: literature review and expert opinion.Journal of neurology · 2023Pooled it
- Reversible white matter changes following a 4-week high phenylalanine exposure in adults with phenylketonuria.Journal of inherited metabolic disease · 2025Trial
- Transient brain structure changes after high phenylalanine exposure in adults with phenylketonuria.Brain : a journal of neurology · 2024Trial
- Review
- White matter microstructure changes across the lifespan: a meta-analysis of longitudinal diffusion MRI studies.bioRxiv : the preprint server for biology · 2025Article
- Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria.Journal of neurodevelopmental disorders · 2025Article
- Impact of gut probiotic metabolites on phenylketonuria.Frontiers in cellular and infection microbiology · 2025Review
- Cognition and wellbeing in middle-aged early treated people with phenylketonuria: Preliminary results and methodological lessons.Molecular genetics and metabolism reports · 2024Article
- No Impairment in Bone Turnover or Executive Functions in Well-Treated Preschoolers with Phenylketonuria-A Pilot Study.Nutrients · 2024Article
- Volumetric brain reductions in adult patients with phenylketonuria and their relationship with blood phenylalanine levels.Journal of neurodevelopmental disorders · 2024Article
- Low bone mineralization in phenylketonuria may be due to undiagnosed metabolic acidosis.Molecular genetics and metabolism reports · 2023Article
- Neurological and imaging phenotypes of adults with untreated phenylketonuria: new cases and literature review.Journal of neurology · 2023Review
- Compromised white matter is related to lower cognitive performance in adults with phenylketonuria.Brain communications · 2023Article
- Cortical thickness and its relationship to cognitive performance and metabolic control in adults with phenylketonuria.Journal of inherited metabolic disease · 2022Article
- Serum glial fibrillary acidic protein and neurofilament light chain in patients with early treated phenylketonuria.Frontiers in neurology · 2022Article
- Optical Coherence Tomography to Assess Neurodegeneration in Phenylalanine Hydroxylase Deficiency.Frontiers in neurology · 2021Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Phenylketonuria (PKU) is a recessive disorder characterized by disruption in the metabolism of the amino acid phenylalanine (Phe). Prior research indicates that individuals with PKU have substantial white matter (WM) compromise. Much less is known about gray matter (GM) in PKU, but a small body of research suggests volumetric differences compared to controls. To date, developmental trajectories of GM structure in individuals with PKU have not been examined, nor have trajectories of WM and GM been examined within a single study. To address this gap in the literature, we compared longitudinal brain development over a three-year period in individuals with PKU (n = 35; 18 male) and typically-developing controls (n = 71; 35 male) aged 7-21 years. Using diffusion tensor imaging (DTI) and structural magnetic resonance imaging (MRI), we observed whole-brain and regional WM differences between individuals with PKU and controls, which were often exacerbated with increasing age. In marked contrast with trajectories of WM development, trajectories of GM development did not differ between individuals with PKU and controls, indicating that neuropathology in PKU is more prominent in WM than GM. Within individuals with PKU, mediation analyses revealed that whole-brain mean diffusivity (MD) and regional MD in the corpus callosum and centrum semiovale mediated the relationship between dietary treatment compliance (i.e., Phe control) and executive abilities, suggesting a plausible neurobiological mechanism by which Phe control may influence cognitive outcomes. Our findings clarify the specificity, timing, and cognitive consequences of whole-brain and regional WM pathology, with implications for treatment and research in PKU.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.