White matter pathology in phenylketonuria
- PMID: 20123467
- DOI: 10.1016/j.ymgme.2009.10.005
White matter pathology in phenylketonuria
Abstract
Early-treated phenylketonuria (PKU) is associated with a range of neuropsychological impairments. Proposed mechanisms for these impairments include dopamine depletion and white matter pathology. Neuroimaging studies demonstrate high-signal intensity in the periventricular white matter in most PKU patients, which can extend into subcortical and frontal regions in more severe cases. A review of histopathology and neuroimaging studies reveals that diffuse white matter pathology in untreated PKU patients is likely to reflect hypomyelination (lack of myelin formation), while in early-treated patients white matter abnormalities observed on magnetic resonance imaging (MRI) is likely to reflect intramyelinic edema. Research demonstrates that this pathology is associated with metabolic control and may be reversed with adherence to a strict low-phenylalanine (Phe) diet. While the functional significance of white matter pathology in PKU is not certain, there is some evidence that these abnormalities are associated with functional impairments when the pathology extends into subcortical and frontal regions.
Crown Copyright 2009. Published by Elsevier Inc. All rights reserved.
Similar articles
-
Are neuropsychological impairments in children with early-treated phenylketonuria (PKU) related to white matter abnormalities or elevated phenylalanine levels?Dev Neuropsychol. 2007;32(2):645-68. doi: 10.1080/87565640701375963. Dev Neuropsychol. 2007. PMID: 17931123
-
Diffusion-weighted MR imaging in patients with phenylketonuria: relationship between serum phenylalanine levels and ADC values in cerebral white matter.Radiology. 2005 Aug;236(2):630-6. doi: 10.1148/radiol.2362040611. Radiology. 2005. PMID: 16040919
-
[Brain white matter lesions of children with phenylketonuria before and after treatment].Zhongguo Dang Dai Er Ke Za Zhi. 2006 Feb;8(1):13-6. Zhongguo Dang Dai Er Ke Za Zhi. 2006. PMID: 16522231 Chinese.
-
White matter disturbances in phenylketonuria: Possible underlying mechanisms.J Neurosci Res. 2021 Jan;99(1):349-360. doi: 10.1002/jnr.24598. Epub 2020 Mar 6. J Neurosci Res. 2021. PMID: 32141105 Review.
-
A comparison of phenylketonuria with attention deficit hyperactivity disorder: do markedly different aetiologies deliver common phenotypes?Brain Res Bull. 2013 Oct;99:63-83. doi: 10.1016/j.brainresbull.2013.10.003. Epub 2013 Oct 16. Brain Res Bull. 2013. PMID: 24140048 Review.
Cited by
-
Correlation of age-specific phenylalanine levels with intellectual outcome in patients with phenylketonuria.J Inherit Metab Dis. 2011 Aug;34(4):963-71. doi: 10.1007/s10545-011-9329-1. Epub 2011 May 10. J Inherit Metab Dis. 2011. PMID: 21556836
-
Impact of phenylalanine on cognitive, cerebral, and neurometabolic parameters in adult patients with phenylketonuria (the PICO study): a randomized, placebo-controlled, crossover, noninferiority trial.Trials. 2020 Feb 13;21(1):178. doi: 10.1186/s13063-019-4022-z. Trials. 2020. PMID: 32054509 Free PMC article.
-
Effects of LC-PUFA Supplementation in Patients with Phenylketonuria: A Systematic Review of Controlled Trials.Nutrients. 2019 Jul 6;11(7):1537. doi: 10.3390/nu11071537. Nutrients. 2019. PMID: 31284588 Free PMC article.
-
Mutation analysis of the PAH gene in phenylketonuria patients from Rio de Janeiro, Southeast Brazil.Mol Genet Genomic Med. 2018 May 10;6(4):575-91. doi: 10.1002/mgg3.408. Online ahead of print. Mol Genet Genomic Med. 2018. PMID: 29749107 Free PMC article.
-
Characterisation and differential diagnosis of neurological complications in adults with phenylketonuria: literature review and expert opinion.J Neurol. 2023 Aug;270(8):3675-3687. doi: 10.1007/s00415-023-11703-4. Epub 2023 Apr 20. J Neurol. 2023. PMID: 37081197 Free PMC article.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical