de los Reyes Emily, Dyken Paul Richard, Phillips Paul, Brodsky Michael, Bates Stephen, Glasier Charles, Mrak Robert E
Department of Pediatrics, University of Arkansas for the Medical Sciences, Little Rock, USA.
J Child Neurol. 2004 Jan;19(1):42-6. doi: 10.1177/08830738040190010703.
The neuronal ceroid-lipofuscinoses are a group of diseases that are characterized by progressive neuroretinal symptomatology, progressive accumulation of autofluorescing waxy lipopigments (ceroid-lipofuscin) within the brain and other tissues, and cerebral atrophy. Juvenile neuronal ceroid-lipofuscinosis, or Batten disease, is a form of neuronal ceroid-lipofuscinosis that is characterized by onset of neuroretinal symptoms between 4 and 10 years. Juvenile neuronal ceroid-lipofuscinosis is the most common type of neuronal ceroid-lipofuscinosis in the United States and Europe and is inherited as an autosomal recessive genetic disorder. Research in the last decade has led to the identification of the responsible gene for juvenile neuronal ceroid-lipofuscinosis, which is designated as CLN3. CLN3 is located on chromosome 16p11.2-12.1. The major mutation is a 1.02 kb deletion, which removes exons 7 and 8. Both homozygotic and heterozygotic deletions at the CLN3 gene site have been associated with the clinical syndromes of juvenile neuronal ceroid-lipofuscinosis. We report a possible atypical case of neuronal ceroid-lipofuscinosis, an infant, who presented at 5 months of age with a lack of developmental milestones, poor vision, severe retinopathy, intractable seizures, and progressive cerebral atrophy. Extensive laboratory investigations, including thorough metabolic evaluations, were unremarkable except for neuroimaging studies, electroencephalography, and electroretinography, all of which showed abnormalities confirming both cerebral and retinal degeneration. Although skin and conjunctival biopsies did not show classic fingerprint cytosomes by electron microscopic study, which characterize juvenile neuronal ceroid-lipofuscinosis, a diagnosis of an atypical form of juvenile neuronal ceroid-lipofuscinosis was suspected on the basis of the clinical picture. The retinal abnormalities, surprisingly, were those believed to be diagnostic of juvenile-onset neuronal ceroid-lipofuscinosis, or Batten disease. Subsequently, a heterozygous mutation for the common 1.02 kb deletion characteristic of juvenile neuronal ceroid-lipofuscinosis was established.
神经元蜡样脂褐质沉积症是一组以进行性神经视网膜症状、大脑及其他组织中自发荧光的蜡样脂色素（蜡样脂褐质）进行性蓄积以及脑萎缩为特征的疾病。青少年型神经元蜡样脂褐质沉积症，即巴滕病，是神经元蜡样脂褐质沉积症的一种形式，其特征为在4至10岁之间出现神经视网膜症状。青少年型神经元蜡样脂褐质沉积症是美国和欧洲最常见的神经元蜡样脂褐质沉积症类型，为常染色体隐性遗传疾病。过去十年的研究已确定青少年型神经元蜡样脂褐质沉积症的致病基因，命名为CLN3。CLN3位于16号染色体的p11.2 - 12.1区域。主要突变是一个1.02 kb的缺失，该缺失去除了第7和第8外显子。CLN3基因位点的纯合和杂合缺失均与青少年型神经元蜡样脂褐质沉积症的临床综合征相关。我们报告了一例可能的非典型神经元蜡样脂褐质沉积症病例，为一名婴儿，5个月大时出现发育里程碑缺失、视力差、严重视网膜病变、顽固性癫痫发作以及进行性脑萎缩。广泛的实验室检查，包括全面的代谢评估，除神经影像学检查、脑电图和视网膜电图外均无异常，所有这些检查均显示异常，证实了脑和视网膜的退化。尽管皮肤和结膜活检在电子显微镜检查中未显示青少年型神经元蜡样脂褐质沉积症所特有的典型指纹状细胞体，但根据临床表现怀疑为青少年型神经元蜡样脂褐质沉积症的非典型形式。令人惊讶的是，视网膜异常被认为是青少年发病的神经元蜡样脂褐质沉积症即巴滕病的诊断依据。随后，确定了青少年型神经元蜡样脂褐质沉积症常见的1.02 kb缺失的杂合突变。
