Bennett Michael J, Rakheja Dinesh
Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Dev Disabil Res Rev. 2013;17(3):254-9. doi: 10.1002/ddrr.1118.
The neuronal ceroid-lipofuscinoses (NCL's, Batten disease) represent a group of severe neurodegenerative diseases, which mostly present in childhood. The phenotypes are similar and include visual loss, seizures, loss of motor and cognitive function, and early death. At autopsy, there is massive neuronal loss with characteristic storage in remaining neurons. Neurons appear to die because of increased rates of apoptosis and altered autophagy. Ten genes have been identified so far that result in an NCL (CLN1-10). The most common forms are CLN1, CLN2, and CLN3, which were previously known as Infantile, Late-Infantile, and Juvenile NCL's, respectively. CLN1 and CLN2 result from mutations in soluble lysosomal enzymes palmitoyl-protein thioesterase (PPT) and tripeptidyl peptidase 1 (TPP1), which can be measured in white blood cells for clinical diagnosis. Molecular diagnostic testing is routinely available for CLN1, CLN2, and CLN3. Sequencing of other NCL genes may be required to establish a diagnosis when the common forms are ruled out. The pathogenesis of NCL neuronal loss resulting from loss of function of any of the NCL gene products remains unknown and no treatment options are presently available.
神经元蜡样脂褐质沉积症（NCLs，巴顿病）是一组严重的神经退行性疾病，大多在儿童期发病。其临床表现相似，包括视力丧失、癫痫发作、运动和认知功能丧失以及过早死亡。尸检时可见大量神经元丢失，剩余神经元中有特征性的储存物。神经元似乎因凋亡率增加和自噬改变而死亡。目前已确定有十个基因会导致NCL（CLN1 - 10）。最常见的类型是CLN1、CLN2和CLN3，它们以前分别被称为婴儿型、晚婴儿型和青少年型NCL。CLN1和CLN2是由可溶性溶酶体酶棕榈酰蛋白硫酯酶（PPT）和三肽基肽酶1（TPP1）的突变引起的，可在白细胞中检测这些酶用于临床诊断。CLN1、CLN2和CLN3通常可进行分子诊断检测。当排除常见类型时，可能需要对其他NCL基因进行测序以明确诊断。由任何一种NCL基因产物功能丧失导致NCL神经元丢失的发病机制尚不清楚，目前也没有治疗方法。
