PDF(Pubmed)
Abstract：
TUBB4A pathogenic variants are associated with a spectrum of neurologic impairments including movement disorders and leukodystrophy. With the development of targeted therapies, there is an urgent unmet need for validated tools to measure mobility impairment. Our aim is to explore gross motor function in a pediatric-onset TUBB4A-related leukodystrophy cohort with existing gross motor outcome tools. Gross Motor Function Measure-88 (GMFM-88), Gross Motor Function Classification System (GMFCS-ER), and Gross Motor Function Classification-Metachromatic Leukodystrophy (GMFC-MLD) were selected through face validity. Subjects with a confirmed clinical and molecular diagnosis of TUBB4A-related leukodystrophy were enrolled. Participants\' sex, age, genotype, and age at disease onset were collected, together with GMFM-88 and concurrent GMFCS-ER and GMFC-MLD. Performances on each measure were compared. GMFM-88 floor effect was defined as total score below 20%. A total of 35 subjects participated. Median performance by GMFM-88 was 16.24% (range 0-97.31), with 42.9% (n = 15) of individuals performing above the floor. GMFM-88 Dimension A (Lying and Rolling) was the best-performing dimension in the GMFM-88 (n = 29 above the floor). All levels of the Classification Scales were represented, with the exception of the GMFC-MLD level 0. Evaluation by GMFM-88 was strongly correlated with the Classification Scales (Spearman correlations: GMFCS-ER:GMFM-88 r = 0.90; GMFC-MLD:GMFM-88 r = 0.88; GMFCS-ER:GMFC-MLD: r = 0.92). Despite overall observation of a floor effect, the GMFM-88 is able to accurately capture the performance of individuals with attenuated phenotypes. GMFM-88 Dimension A shows no floor effect. GMFC-MLD shows a strong correlation with GMFCS-ER and GMFM-88, supporting its use as an age-independent functional score in TUBB4A-related leukodystrophy.
摘要：
TUBB4A致病变体与一系列神经损伤相关，包括运动障碍和脑白质营养不良。随着靶向治疗的发展,对衡量流动性损害的经过验证的工具存在迫切的未满足的需求。我们的目的是利用现有的粗大运动结果工具，在儿科发病TUBB4A相关的脑白质营养不良队列中探索粗大运动功能。粗大运动功能测量-88(GMFM-88),粗大运动功能分类系统(GMFCS-ER),和粗大运动功能分类-异嗜性白细胞营养不良（GMFC-MLD）通过面部有效性进行选择。纳入具有经证实的TUBB4A相关脑白质营养不良的临床和分子诊断的受试者。参与者性，年龄,基因型，收集发病时的年龄，连同GMFM-88和并发的GMFCS-ER和GMFC-MLD。比较了每种措施的性能。GMFM-88地板效应定义为总分低于20%。共有35名受试者参加。GMFM-88的平均性能为16.24%（范围0-97.31），42.9%(n=15)的人在地板以上表现。GMFM-88尺寸A（说谎和滚动）是GMFM-88中性能最好的尺寸（地板上方n=29）。表示了分类量表的所有级别，除了GMFC-MLD级别为0。GMFM-88的评估与分类量表密切相关（斯皮尔曼相关性：GMFCS-ER：GMFM-88r=0.90；GMFC-MLD：GMFM-88r=0.88；GMFCS-ER：GMFC-MLD：r=0.92）。尽管总体上观察到了地板效应，GMFM-88能够准确捕获具有减毒表型的个体的表现。GMFM-88尺寸A没有显示地板效果。GMFC-MLD显示出与GMFCS-ER和GMFM-88的强相关性，支持将其用作TUBB4A相关脑白质营养不良的年龄无关功能评分。
