Department of Child Neurology, Children's Hospital, University of Tübingen, Hoppe-Seyler-Str. 1, 72072, Tübingen, Germany.
Section for Experimental MR of the CNS, Department of Child Neurology and Neuroradiology, University of Tübingen, Tübingen, Germany.
Orphanet J Rare Dis. 2020 Sep 10;15(1):243. doi: 10.1186/s13023-020-01489-3.
Krabbe disease or globoid cell leukodystrophy is a severe neurodegenerative disorder caused by a defect in the GALC gene leading to a deficiency of the enzyme ß-galactocerebrosidase. The aim of this work was to describe the natural disease course covering the whole spectrum of the disease.
Natural history data were collected with a standardized questionnaire, supplemented by medical record data. We defined different forms of the disease according to Abdelhalim et al. (2014). Developmental and disease trajectories were described based on the acquisition and loss of milestones as well as the time of first clearly identifiable symptoms and needs such as spasticity, seizures and tube feeding. MRI was assessed using the scoring system by Loes et al. (1999) and in addition a pattern recognition approach, based on Abdelhalim et al. (2014).
Thirty-eight patients were identified, from 27 of these patients 40 MRIs were available; 30 (79%) had an infantile onset, showing first symptoms in their first year of life, almost all (27 out of 30) starting in the first six months. A later onset after the first year of life was observed in 8 patients (21%, range 18 months to 60 years). Irritability, abnormalities in movement pattern as well as general developmental regression were the first symptoms in the infantile group; disease course was severe with rapid progression, e.g. loss of visual fixation, need for tube feeding and then an early death. Gait disorders were the first symptoms in all patients of the later onset groups; progression was variable. The different forms of the disease were characterized by different MRI patterns (infantile: diffuse white matter involvement and cerebellar structures specifically affected, later onset: parieto-occipital white matter and splenium affected, adult: motor tracts specifically affected).
This is the first description of the natural history of Krabbe disease in a larger European cohort using developmental, clinical and MRI data. We would like to highlight the very different clinical and MRI characteristics of the later onset forms. These data are important for counselling affected patients and families and may serve as a basis for future treatment trials.
克拉伯病或球样细胞脑白质营养不良是一种严重的神经退行性疾病，由 GALC 基因缺陷导致β-半乳糖脑苷脂酶缺乏引起。本研究旨在描述疾病的自然病程，涵盖疾病的全貌。
采用标准化问卷收集自然病史数据，并补充病历数据。我们根据 Abdelhalim 等人（2014 年）的定义，将疾病分为不同的形式。根据获得和丧失里程碑以及首次出现明确可识别症状和需求（如痉挛、癫痫发作和管饲）的时间，描述发育和疾病轨迹。采用 Loes 等人（1999 年）的评分系统评估 MRI，并采用基于 Abdelhalim 等人（2014 年）的模式识别方法。
共确定了 38 例患者，其中 27 例患者有 40 例 MRI 可供分析；30 例（79%）为婴儿期起病，在生命的第一年出现首发症状，几乎所有（30 例中的 27 例）均在头 6 个月发病。8 例（21%，范围 18 个月至 60 岁）为起病晚于 1 岁。婴儿组的首发症状为易激惹、运动模式异常和全面发育迟缓；疾病进展迅速，如视力丧失、需要管饲，然后早亡，病情严重。步态障碍为所有晚发型患者的首发症状；进展情况各异。不同形式的疾病具有不同的 MRI 特征（婴儿型：弥漫性白质受累，小脑结构特别受累；晚发型：顶枕叶白质和胼胝体受累；成人型：运动束特别受累）。
这是使用发育、临床和 MRI 数据首次对欧洲较大克拉伯病队列的自然史进行描述。我们想强调晚发型疾病的临床表现和 MRI 特征差异很大。这些数据对于咨询受影响的患者及其家属非常重要，并可能成为未来治疗试验的基础。
