Gowda Vykuntaraju K, Vegda Hemadri, Sugumar Kiruthiga, Narayanappa Gayathri, Srinivasan Varunvenkat M, Santhoshkumar Rashmi, Bhat Maya, Balu Sam, Naveen Mohan Rao
Department of Pediatric Neurology, Indira Gandhi Institute of Child Health, Bangalore, India.
Department of Neuropathology, National Institute of Mental Health and Neurosciences, Bangalore, India.
J Pediatr Genet. 2020 Aug 4;10(4):266-273. doi: 10.1055/s-0040-1715575. eCollection 2021 Dec.
Neuronal ceroid Lipofuscinosis (NCL), inherited disorders of lysosomal storage disorders, constitute the most common progressive encephalopathies with an incidence of 1.3 to 7 in 100,000 live births. We reported clinical, electrophysiological, radiological, ultrastructural, and molecular genetic features of NCL. This is a retrospective review, in a tertiary care center from January 2016 to December 2019. All children with clinical features of NCL and confirmed by pathogenic mutation and/or enzyme assay were included. A total of 60 children (male:female = 3:1) were studied. The commonest type was CLN 2 (41.7%). Neuroregression, seizures, and ataxia were present in all cases. Retinal arterial attenuation was seen in 38.33% cases. Magnetic resonance imaging (MRI) brain was abnormal in all patients, thalamic and caudate nucleus atrophy common in CLN1 (62%). Electroencephalography was abnormal in all children, but photoparoxysmal response at low intermittent photic stimulation frequencies was seen in four children of CLN2. Electron microscopy done in 43 children revealed abnormal inclusions in 20 (46.52%) children. Enzyme study showed low levels in 36 (78%) out of 46 cases. Of these, 21 had low tripeptidyl peptidase and 15 had low palmitoyl protein thioesterase levels. Molecular testing done in 26 cases showed pathogenic variant in 23 (88%) cases. Infantile onset with thalamic atrophy on MRI is common in CLN1 and refractory epilepsy, visual impairment and specific EEG changes are common in CLN2. These features are helpful in selecting enzyme assay for CLN1 versus CLN2. Electron microscopy helped in the diagnosis and genetic testing in subtyping. Thus, a multimode approach played a role in the diagnosis of NCL.
神经元蜡样脂褐质沉积症(NCL)是溶酶体贮积症的遗传性疾病,是最常见的进行性脑病,活产发病率为十万分之1.3至7。我们报告了NCL的临床、电生理、放射学、超微结构和分子遗传学特征。这是一项在2016年1月至2019年12月于三级医疗中心进行的回顾性研究。纳入所有具有NCL临床特征并经致病突变和/或酶测定确诊的儿童。共研究了60名儿童(男:女 = 3:1)。最常见的类型是CLN 2(41.7%)。所有病例均出现神经功能倒退、癫痫发作和共济失调。38.33%的病例可见视网膜动脉变细。所有患者的脑部磁共振成像(MRI)均异常,CLN1中丘脑和尾状核萎缩常见(62%)。所有儿童的脑电图均异常,但CLN2的4名儿童在低间歇性光刺激频率下出现光阵发性反应。43名儿童进行了电子显微镜检查,其中20名(46.52%)儿童发现异常包涵体。酶学研究显示46例中有36例(78%)水平较低。其中,21例三肽基肽酶水平低,15例棕榈酰蛋白硫酯酶水平低。26例进行了分子检测,23例(88%)显示致病变异。CLN1中常见婴儿期起病且MRI显示丘脑萎缩,CLN2中难治性癫痫、视力障碍和特定脑电图改变常见。这些特征有助于为CLN1和CLN2选择酶学检测方法。电子显微镜有助于诊断和亚型的基因检测。因此,多模式方法在NCL的诊断中发挥了作用。