Volumetric brain reductions in adult patients with phenylketonuria and their relationship with blood phenylalanine levels.

IF 4.1 2区医学 Q1 CLINICAL NEUROLOGY Journal of Neurodevelopmental Disorders Pub Date : 2024-06-21 DOI:10.1186/s11689-024-09553-w

Jèssica Pardo, Clara Capdevila-Lacasa, Bàrbara Segura, Adriana Pané, Cristina Montserrat, Maria de Talló Forga-Visa, Pedro J Moreno, Glòria Garrabou, Josep M Grau-Junyent, Carme Junqué

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Abstract

Background: Continued dietary treatment since early diagnosis through newborn screening programs usually prevents brain-related complications in phenylketonuria (PKU). However, subtle neurocognitive and brain alterations may be observed in some adult patients despite early treatment. Nevertheless, neuropsychological and neuroimaging studies in the field remain scarce.

Objectives: This work aimed to determine possible neuropsychological and structural brain alterations in treated adult patients with PKU.

Methods: Thirty-five patients with PKU and 22 healthy controls (HC) underwent neuropsychological assessment and T1-weighted magnetic resonance imaging on a 3 T scanner. FreeSurfer (v.7.1) was used to obtain volumetric measures and SPSS (v27.0.1.0) was used to analyze sociodemographic, neuropsychological, volumetric, and clinical data (p < 0.05).

Results: Adult patients with PKU showed significantly lower performance than HC in Full Scale IQ (t = 2.67; p = .010) from the WAIS-IV. The PKU group also showed significantly lower volumes than HC in the pallidum (U = 224.000; p = .008), hippocampus (U = 243.000; p = .020), amygdala (U = 200.000; p = .002), and brainstem (t = 3.17; p = .006) as well as in total cerebral white matter volume (U = 175.000; p = .001). Blood phenylalanine (Phe) levels in PKU patients were negatively correlated with the pallidum (r = -0.417; p = .013) and brainstem (r = -0.455, p = .006) volumes.

Conclusions: Adult patients with early-treated PKU showed significantly lower global intelligence than HC. Moreover, these patients showed reduced global white matter volume as well as reductions in the volume of several subcortical grey matter structures, which might be related to the existence of underlying neurodevelopmental alterations. Higher blood Phe levels were also negatively correlated with pallidum and brainstem, suggesting a higher vulnerability of these structures to Phe toxicity.

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苯丙酮尿症成年患者脑容量减少及其与血苯丙氨酸水平的关系。

背景：自通过新生儿筛查项目进行早期诊断以来，持续的饮食治疗通常可以预防苯丙酮尿症（PKU）与脑有关的并发症。然而，尽管进行了早期治疗，在一些成年患者中仍可观察到微妙的神经认知和脑部改变。然而，该领域的神经心理学和神经影像学研究仍然很少：本研究旨在确定接受治疗的成年 PKU 患者可能出现的神经心理学和脑结构改变：35名PKU患者和22名健康对照组（HC）在3T扫描仪上接受了神经心理学评估和T1加权磁共振成像。FreeSurfer（v.7.1）用于获取容积测量数据，SPSS（v27.0.1.0）用于分析社会人口学、神经心理学、容积测量和临床数据（P 结果：在WAIS-IV中，成年PKU患者的全量表智商表现明显低于HC（t = 2.67; p = .010）。PKU 组的苍白球（U = 224.000；p = .008）、海马（U = 243.000；p = .020）、杏仁核（U = 200.000；p = .002）和脑干（t = 3.17；p = .006）以及大脑白质总体积（U = 175.000；p = .001）也明显低于 HC 组。PKU患者的血液苯丙氨酸（Phe）水平与苍白球（r = -0.417；p = .013）和脑干（r = -0.455，p = .006）体积呈负相关：结论：早期治疗的成年北京大学患者的整体智力明显低于普通人。结论：早期治疗的北京大学成年患者的总体智力明显低于普通人群，而且这些患者的总体白质体积减少，皮层下灰质结构的体积也有所减少，这可能与潜在的神经发育改变有关。血液中较高的 Phe 水平还与苍白球和脑干呈负相关，这表明这些结构更容易受到 Phe 毒性的影响。

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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.