Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria
Abstract Background Altered white matter (WM) is consistently reported in patients with phenylketonuria (PKU). However, the knowledge about WM microstructural integrity in early-treated adults with classical PKU and its relationship with cognition and metabolic parameters is inconclusive. This study...
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| Language: | English |
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BMC
2025-07-01
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| Series: | Journal of Neurodevelopmental Disorders |
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| Online Access: | https://doi.org/10.1186/s11689-025-09622-8 |
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| author | Jèssica Pardo Clara Capdevila-Lacasa Bàrbara Segura Adriana Pané Pedro J. Moreno Glòria Garrabou Josep M. Grau-Junyent Carme Junqué Consortium PKU.cat |
| author_facet | Jèssica Pardo Clara Capdevila-Lacasa Bàrbara Segura Adriana Pané Pedro J. Moreno Glòria Garrabou Josep M. Grau-Junyent Carme Junqué Consortium PKU.cat |
| author_sort | Jèssica Pardo |
| collection | DOAJ |
| description | Abstract Background Altered white matter (WM) is consistently reported in patients with phenylketonuria (PKU). However, the knowledge about WM microstructural integrity in early-treated adults with classical PKU and its relationship with cognition and metabolic parameters is inconclusive. This study aims to explore the cerebral WM microstructural alterations in adult patients with early-treated classical PKU and their association with blood phenylalanine (Phe) levels and neuropsychological performance using whole-brain diffusion tensor imaging (DTI). Methods Twenty-nine patients with early-treated classical PKU (mean age = 30.86, SD = 7.74) and 31 healthy controls (mean age = 32.45, SD = 9.40) underwent neuropsychological assessment and MRI. Phe dry blood spot (DBS-Phe) samples, along with venous Phe levels, were collected from the PKU sample to calculate the index of dietary control (IDC). Tract-based spatial statistics (TBSS) of the mean diffusivity (MD), and fractional anisotropy (FA), were carried out with FSL v6.0.4 to assess between-group differences and to explore associations with both cognitive and clinical data. Results Patients exhibited a widespread white matter tract involvement, with lower MD and higher FA values compared to controls. The most affected tracts were the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus for MD, and the anterior corona radiata, uncinate fasciculus and forceps minor for FA. MD negatively correlated with IDC and venous Phe levels, whereas FA negatively correlated with full-scale intelligence quotient (FSIQ) (p-value ≤0.05 FWE-corrected). Conclusions Microstructural WM alterations were present in adults with early-treated classical PKU, and these abnormalities were related to global intelligence and metabolic control markers. Although our results suggest the importance of proper disease management, further studies are needed to determine its long-term relevance. |
| format | Article |
| id | doaj-art-3adf2624d7dc4e5a86043992e473b57b |
| institution | Kabale University |
| issn | 1866-1955 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neurodevelopmental Disorders |
| spelling | doaj-art-3adf2624d7dc4e5a86043992e473b57b2025-08-20T03:45:22ZengBMCJournal of Neurodevelopmental Disorders1866-19552025-07-0117111210.1186/s11689-025-09622-8Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuriaJèssica Pardo0Clara Capdevila-Lacasa1Bàrbara Segura2Adriana Pané3Pedro J. Moreno4Glòria Garrabou5Josep M. Grau-Junyent6Carme Junqué7Consortium PKU.catMedical Psychology Unit, Department of Medicine, Institute of Neurosciences, University of BarcelonaMedical Psychology Unit, Department of Medicine, Institute of Neurosciences, University of BarcelonaMedical Psychology Unit, Department of Medicine, Institute of Neurosciences, University of BarcelonaBiomedical Research Networking Center on Physiopathology of Obesity and Nutrition (CIBEROBN)Muscular and Inherited Metabolic Disorders Adults Unit, Hospital Clínic de BarcelonaMuscular and Inherited Metabolic Disorders Adults Unit, Hospital Clínic de BarcelonaFundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi i Sunyer (FRCB-IDIBAPS)Medical Psychology Unit, Department of Medicine, Institute of Neurosciences, University of BarcelonaAbstract Background Altered white matter (WM) is consistently reported in patients with phenylketonuria (PKU). However, the knowledge about WM microstructural integrity in early-treated adults with classical PKU and its relationship with cognition and metabolic parameters is inconclusive. This study aims to explore the cerebral WM microstructural alterations in adult patients with early-treated classical PKU and their association with blood phenylalanine (Phe) levels and neuropsychological performance using whole-brain diffusion tensor imaging (DTI). Methods Twenty-nine patients with early-treated classical PKU (mean age = 30.86, SD = 7.74) and 31 healthy controls (mean age = 32.45, SD = 9.40) underwent neuropsychological assessment and MRI. Phe dry blood spot (DBS-Phe) samples, along with venous Phe levels, were collected from the PKU sample to calculate the index of dietary control (IDC). Tract-based spatial statistics (TBSS) of the mean diffusivity (MD), and fractional anisotropy (FA), were carried out with FSL v6.0.4 to assess between-group differences and to explore associations with both cognitive and clinical data. Results Patients exhibited a widespread white matter tract involvement, with lower MD and higher FA values compared to controls. The most affected tracts were the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus for MD, and the anterior corona radiata, uncinate fasciculus and forceps minor for FA. MD negatively correlated with IDC and venous Phe levels, whereas FA negatively correlated with full-scale intelligence quotient (FSIQ) (p-value ≤0.05 FWE-corrected). Conclusions Microstructural WM alterations were present in adults with early-treated classical PKU, and these abnormalities were related to global intelligence and metabolic control markers. Although our results suggest the importance of proper disease management, further studies are needed to determine its long-term relevance.https://doi.org/10.1186/s11689-025-09622-8PhenylketonuriaNeuropsychological performanceDiffusion tensor imagingCerebral white matterDietary control |
| spellingShingle | Jèssica Pardo Clara Capdevila-Lacasa Bàrbara Segura Adriana Pané Pedro J. Moreno Glòria Garrabou Josep M. Grau-Junyent Carme Junqué Consortium PKU.cat Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria Journal of Neurodevelopmental Disorders Phenylketonuria Neuropsychological performance Diffusion tensor imaging Cerebral white matter Dietary control |
| title | Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria |
| title_full | Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria |
| title_fullStr | Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria |
| title_full_unstemmed | Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria |
| title_short | Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria |
| title_sort | diffusivity alterations related to cognitive performance and phenylalanine levels in early treated adults with phenylketonuria |
| topic | Phenylketonuria Neuropsychological performance Diffusion tensor imaging Cerebral white matter Dietary control |
| url | https://doi.org/10.1186/s11689-025-09622-8 |
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