PDF(Pubmed)
Abstract：
Wolfram syndrome is a rare disease caused by pathogenic variants in the WFS1 gene with progressive neurodegeneration. As an easily accessible biomarker of progression of neurodegeneration has not yet been found, accurate tracking of the neurodegenerative process over time requires assessment by costly and time-consuming clinical measures and brain magnetic resonance imaging (MRI). A blood-based measure of neurodegeneration, neurofilament light chain (NfL), is relatively inexpensive and can be repeatedly measured at remote sites, standardized, and measured in individuals with MRI contraindications. To determine whether NfL levels may be of use in disease monitoring and reflect disease activity in Wolfram syndrome, plasma NfL levels were compared between children and young adults with Wolfram syndrome (n = 38) and controls composed of their siblings and parents (n = 35) and related to clinical severity and selected brain region volumes within the Wolfram group. NfL levels were higher in the Wolfram group [median (interquartile range) NfL = 11.3 (7.8-13.9) pg/mL] relative to controls [5.6 (4.5-7.4) pg/mL]. Within the Wolfram group, higher NfL levels related to worse visual acuity, color vision and smell identification, smaller brainstem and thalamic volumes, and faster annual rate of decrease in thalamic volume over time. Our findings suggest that plasma NfL levels can be a powerful tool to non-invasively assess underlying neurodegenerative processes in children, adolescents and young adults with Wolfram syndrome.
摘要：
Wolfram综合征是由WFS1基因致病变异所惹起的进行性神经变性的罕见疾病。作为一种容易获得的神经变性进展的生物标志物，尚未发现，随着时间的推移准确跟踪神经退行性过程需要通过昂贵且耗时的临床措施和脑磁共振成像（MRI）进行评估。以血液为基础的神经变性的测量，神经丝轻链（NfL），相对便宜，可以在远程站点重复测量，标准化，并在有MRI禁忌症的个体中测量。为了确定NfL水平是否可用于疾病监测并反映Wolfram综合征的疾病活动，比较了患有Wolfram综合征的儿童和年轻人（n=38）与由其兄弟姐妹和父母组成的对照组（n=35）之间的血浆NfL水平，并与Wolfram组中的临床严重程度和选定的大脑区域体积有关。相对于对照组[5.6（4.5-7.4）pg/mL]，Wolfram组[中位数（四分位距）NfL=11.3（7.8-13.9）pg/mL]的NfL水平更高。在Wolfram集团内部,较高的NfL水平与较差的视力有关，颜色视觉和气味识别，脑干和丘脑体积较小，随着时间的推移，丘脑体积的年下降速度更快。我们的研究结果表明，血浆NfL水平可以成为非侵入性评估儿童潜在神经退行性过程的有力工具。青少年和青少年Wolfram综合征。
