Natural history of Krabbe disease - a nationwide study in Germany using clinical and MRI data
Natural history of Krabbe disease - a nationwide study in Germany using clinical and MRI data
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DOI：
10.1186/s13023-020-01489-3
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发表时间：
2020-09-10
影响因子：
3.7
通讯作者：
Kehrer, Christiane
中科院分区：
文献类型：
--
作者：
Krieg, Sarah Isabel;Kraegeloh-Mann, Ingeborg;Kehrer, Christiane
背景Krabbe病或球状细胞白质营养不良症是一种由GALC基因缺陷导致酶SS-半乳糖脑苷酶缺陷引起的严重的神经退行性疾病。这项工作的目的是描述涵盖所有疾病范围的自然疾病过程。方法采用标准化问卷收集自然病史资料，并辅以病历资料。我们根据Abdelhalim等人对疾病的不同形式进行了定义。(2014)。根据里程碑的获得和丢失以及首次明确识别的症状和需要的时间，如痉挛、癫痫发作和管饲，描述了发育和疾病的轨迹。使用Loes等人的评分系统对MRI进行评估。(1999)以及基于Abdelhalim等人的模式识别方法。(2014)。结果共确诊38例，其中27例有40项磁共振检查，其中30例(79%)为婴儿期起病，在出生后第一年出现首发症状，几乎所有患者(27/30)都是从出生后6个月开始发病。有8名患者(21%，18个月至60岁)在出生一年后发病较晚。婴儿组的首发症状为易怒、运动模式异常和全身发育减退；病程严重，进展快，如视觉注视丧失，需要管饲，然后早期死亡。步态障碍是所有较晚起病组患者的首发症状；进展情况各不相同。不同类型的疾病具有不同的MRI表现(婴儿期：弥漫性白质受累，小脑结构特异性受累，晚发性：顶枕白质和压部受累，成人：运动束特异性受累)。结论这是首次在更大的欧洲队列中使用发育、临床和MRI数据描述Krabbe病的自然病史。我们想要强调的是，较晚发病形式的临床和MRI特征截然不同。这些数据对咨询受影响的患者和家属很重要，并可作为未来治疗试验的基础。
Background Krabbe disease or globoid cell leukodystrophy is a severe neurodegenerative disorder caused by a defect in theGALCgene 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. Methods 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). Results 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). Conclusion 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.