Diffusivity alterations related to cognitive performance and phenylalanine levels in early-treated adults with phenylketonuria.

IF 4.1 2区医学 Q1 CLINICAL NEUROLOGY

Journal of Neurodevelopmental Disorders Pub Date : 2025-07-02 DOI:10.1186/s11689-025-09622-8

Jèssica Pardo, Clara Capdevila-Lacasa, Bàrbara Segura, Adriana Pané, Pedro J Moreno, Glòria Garrabou, Josep M Grau-Junyent, Carme Junqué

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引用次数: 0

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.

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早期治疗的苯丙酮尿症患者的认知能力和苯丙氨酸水平与弥散性改变相关

背景：白质（WM）改变在苯丙酮尿症（PKU）患者中一直有报道。然而，早期治疗的典型PKU成人WM显微结构完整性及其与认知和代谢参数的关系尚无定论。本研究旨在利用全脑弥散张量成像（DTI）技术探讨早期治疗的典型PKU成年患者脑WM微结构改变及其与血液苯丙氨酸（Phe）水平和神经心理表现的关系。方法：29例早期治疗的经典PKU患者（平均年龄30.86岁，SD = 7.74）和31例健康对照（平均年龄32.45岁，SD = 9.40）行神经心理评估和MRI检查。从PKU样本中采集Phe干血斑（DBS-Phe）样本以及静脉Phe水平，计算饮食控制指数（IDC）。采用FSL v6.0.4软件对平均扩散系数（MD）和分数各向异性（FA）进行基于束的空间统计（TBSS），以评估组间差异，并探讨其与认知和临床数据的关联。结果：患者表现出广泛的白质束受累，与对照组相比，MD值较低，FA值较高。MD受影响最大的束是下纵束和额枕下束，FA受影响最大的束是前辐射冠、钩状束和小束。MD与IDC和静脉Phe水平呈负相关，FA与全量表智商（FSIQ）呈负相关（经fwe校正后p值≤0.05）。结论：早期治疗的典型PKU患者存在微结构WM改变，这些异常与整体智力和代谢控制标志物有关。虽然我们的结果提示了适当的疾病管理的重要性，但需要进一步的研究来确定其长期相关性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Neurodevelopmental Disorders 医学-临床神经学

CiteScore

7.60

自引率

4.10%

发文量

审稿时长

>12 weeks

期刊介绍： Journal of Neurodevelopmental Disorders is an open access journal that integrates current, cutting-edge research across a number of disciplines, including neurobiology, genetics, cognitive neuroscience, psychiatry and psychology. The journal’s primary focus is on the pathogenesis of neurodevelopmental disorders including autism, fragile X syndrome, tuberous sclerosis, Turner Syndrome, 22q Deletion Syndrome, Prader-Willi and Angelman Syndrome, Williams syndrome, lysosomal storage diseases, dyslexia, specific language impairment and fetal alcohol syndrome. With the discovery of specific genes underlying neurodevelopmental syndromes, the emergence of powerful tools for studying neural circuitry, and the development of new approaches for exploring molecular mechanisms, interdisciplinary research on the pathogenesis of neurodevelopmental disorders is now increasingly common. Journal of Neurodevelopmental Disorders provides a unique venue for researchers interested in comparing and contrasting mechanisms and characteristics related to the pathogenesis of the full range of neurodevelopmental disorders, sharpening our understanding of the etiology and relevant phenotypes of each condition.