SynthesisOrphanet journal of rare diseases2018
White matter microstructural damage in early treated phenylketonuric patients.
Synthesis in Orphanet journal of rare diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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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
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 26 citations in OpenAlex.
- Characterisation and differential diagnosis of neurological complications in adults with phenylketonuria: literature review and expert opinion.Journal of neurology · 2023Pooled it
- Effects of LC-PUFA Supplementation in Patients with Phenylketonuria: A Systematic Review of Controlled Trials.Nutrients · 2019Pooled it
- Reversible white matter changes following a 4-week high phenylalanine exposure in adults with phenylketonuria.Journal of inherited metabolic disease · 2025Trial
- Improved dietary control results in improvements in indices of white matter structure in adults with phenylketonuria: the ReDAPT study.Acta neuropsychiatrica · 2026Article
- Review
- Blood phenylalanine lowering partially reverses white matter changes in a mouse model of phenylketonuria.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria.Journal of neurodevelopmental disorders · 2025Article
- Cognition and wellbeing in middle-aged early treated people with phenylketonuria: Preliminary results and methodological lessons.Molecular genetics and metabolism reports · 2024Article
- Volumetric brain reductions in adult patients with phenylketonuria and their relationship with blood phenylalanine levels.Journal of neurodevelopmental disorders · 2024Article
- Phenylketonuria: A Scoring System for Brain Magnetic Resonance Imaging.Turkish archives of pediatrics · 2023Article
- Compromised white matter is related to lower cognitive performance in adults with phenylketonuria.Brain communications · 2023Article
- High phenylalanine concentrations induce demyelination and microglial activation in mouse cerebellar organotypic slices.Frontiers in neuroscience · 2022Article
- Optical Coherence Tomography to Assess Neurodegeneration in Phenylalanine Hydroxylase Deficiency.Frontiers in neurology · 2021Article
- Sustained Correction of a Murine Model of Phenylketonuria following a Single Intravenous Administration of AAVHSC15-PAH.Molecular therapy. Methods & clinical development · 2020Article
- Determining factors of the cognitive outcome in early treated PKU: A study of 39 pediatric patients.Molecular genetics and metabolism reports · 2019Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite dietary intervention, individuals with early treated phenylketonuria (ETPKU) could present neurocognitive deficits and white matter (WM) abnormalities. The aim of the present study was to evaluate the microstructural integrity of WM pathways across the whole brain in a cohort of paediatric ETPKU patients compared with healthy controls (HCs), by collecting DTI-MRI (diffusion tensor magnetic resonance imaging) data and diffusion values (mean diffusivity (MD), radial diffusivity (RD) and fractional anisotropy (FA)).
methodsDTI-MRI data and diffusion values (MD, RD, FA) from WM tracts across the whole brain were analized using Tract Based Spatial Statistics (TBSS), in 15 paediatrics TPKU patients (median age: 12 years) and compared with 11 HCs. Areas showing abnormal values in the patient group were correlated (Pearson) with age, lifetime Phe values, last year median and mean Phe, concurrent Phe values in plasma, urine neurotransmitters status biomarkers, and with a processing speed task.
resultsETPKU showed bilaterally decreased MD values compared with HCs in the body and splenium of the corpus callosum, superior longitudinal fasciculus, corona radiata and in the posterior limb of the internal capsule. RD values followed a similar pattern, although decreased RD values in PKU patients were also found in the anterior limb of the internal capsule and in the cerebral peduncle. Decreased MD and RD values within the aforementioned regions had significant negative correlations with age, last year median and mean Phe and concurrent Phe values. No correlations were found with monoamines in urine or processing speed task.
conclusionsETPKU patients showed MD and RD values significantly decreased across the whole brain when compared with HCs, and this damage was associated with high Phe values and the age of patients. Despite this microstructural damage, no affectation in processing speed was observed in patients with good metabolic control. DTI-MRI sequences could be used as a technique to quantify WM damage that is difficult to be detect in T1 or T2-weighted images, but also to quantify damage of WM through the follow up of patients with poor metabolic control in prospective studies.
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