晚期婴儿神经元样脂褐质病:CLN2突变患者临床病程的定量描述。

Robert Steinfeld, Peter Heim, Henning von Gregory, Kerstin Meyer, Kurt Ullrich, Hans H Goebel, Alfried Kohlschütter
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引用次数: 149

摘要

我们检查了26例具有晚期婴儿神经性神经样脂褐质病(LINCL)临床和电镜征象的个体。在22例中,我们发现了两个致病等位基因。16例患者仅携带一种或两种常见突变R208X和IVS5-1G > c的组合。在其余病例中,可以检测到四种错义突变,其中R127Q、N286S和T353P是以前未被描述的新等位基因。临床表现评分是通过评估运动、视觉和语言功能以及在疾病过程中每隔3个月的脑癫痫发作发生率来制定的。残疾总分是由运动、视觉和语言功能的单项得分相加得出的。将具有两种常见突变的16个个体分组在一起(称为标准患者),计算第5、第50和第95百分位,并随时间绘制图形。运动功能和语言能力的分数下降最早,在标准患者中进展非常相似。两名N286S突变儿童的表现曲线在95百分位后略有偏离。然而,一名携带R127Q突变的非典型LINCL患者的表现曲线远远超过了第95百分位。所提出的表现评分清晰定量地描述了LINCL患者的病程,因此为临床评估未来的治疗干预措施提供了有用的工具。此外,所描述的性能评分系统可应用于其他类型的神经元类脂褐质病,并可适用于儿童的各种其他神经退行性疾病。
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Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations.

We examined 26 individuals with clinical and electron microscopic signs of late infantile neuronal ceroid lipofuscinosis (LINCL). In 22 cases, we found both pathogenic alleles. Sixteen patients exclusively carried either one or a combination of the two common mutations R208X and IVS5-1G > C. In the remaining cases, four missense mutations could be detected, of which R127Q, N286S, and T353P represent novel, previously not described alleles. A clinical performance score was developed by rating motor, visual, and verbal functions and the incidence of cerebral seizures in 3-month intervals during the course of the disease. A Total Disability Score was derived by summing up the single scores for motor, visual, and verbal functions. The 16 individuals with the two common mutations were grouped together (referred to as standard patients), and the 5th, 50th, and 95th centiles were calculated and graphically depicted over time. The scores for motor function and language ability dropped earliest and progressed very similarly in the standard patients. The performance curves of two children with the N286S mutation slightly diverged from the 95th centile. However, the performance curves of one patient with atypical LINCL carrying the R127Q mutation fell far beyond the 95th centile. The presented performance rating clearly and quantitatively delineates the disease course of the LINCL patients and hence offers a useful tool for clinical evaluation of future therapeutic interventions. In addition, the described performance score system can be applied to other types of neuronal ceroid lipofuscinoses and could be adapted to various other neurodegenerative diseases of childhood.

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