Longitudinal Studies in Batten Disease

巴顿病的纵向研究

• 批准号: 7885737
• 负责人: JONATHAN W. MINK
• 金额: $ 4.82万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7885737
• 关键词: Adolescent; Affect; Age; Age of Onset; Aggressive behavior; Anxiety; Behavioral; Blindness; Caregiver Burden; Cessation of life; Child; Childhood; Clinical Trials; Data; Dementia; Disabled Persons; Disease; Genotype; Hallucinations; Incidence; Individual; Inherited; Language; Life; Longitudinal Studies; Lysosomal Storage Diseases; Motor Skills; Mutation; Natural History; Neurodegenerative Disorders; Neurologic; Neuronal Ceroid-Lipofuscinosis; Obsession; Personality; Phenotype; Rare Diseases; Research; Seizures; Self Care; Speech; Spielmeyer-Vogt Disease; Symptoms; Validity and Reliability; Variant; disability; neuropsychological; skills; translational clinical trial

The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are inherited, autosomal recessive lysosomal storage diseases. Although the NCLs are relatively rare, the childhood variants represent the most common neurodegenerative disorders of childhood, affecting approximately 1:25,000 in the U.S. and with an incidence worldwide as high as 1:12,500. NCL variants are distinguished mainly by their different ages of onset and the rate at which symptoms progress. Juvenile NCL (JNCL), due to the CLN-3 mutation, is one of the more common forms of NCL. Symptom onset for JNCL is between ages 5 to 8, with slow progression until death in the 2nd or 3rd decade of life. The most common early symptoms of JNCL are vision loss, seizures dementia, behavioral difficulties, and impaired motor skills. As the disease progresses, the child becomes increasingly disabled and there is a substantial caregiver burden. There are few quantitative data on the natural history of JNCL. It is known that JNCL includes a broad range of neurological, neuropsychological, and behavioral/psychiatric symptoms. There is progressive loss of speech, language, motor skills, and self-care skills as the disease progresses. In some individuals, aggressive behavior, anxiety, hallucinations, obsessions, or personality changes are prominent. However, it is not known to what degree each type of symptoms contributes to the overall disability and caregiver burden. It is also not known to what degree the seizures and seizure control contributes to disability. Further, it is not known to what extent genotype influences phenotypic variability. We propose three specific aims to determine the natural history of JNCL quantitatively, to characterize the neuropsychological and behavioral phenotype of JNCL, to establish validity and reliability of a rating scale for JNCL, and to determine correlations between phenotype and genotype of individual JNCL subjects. Successful completion of this project will provide the necessary framework for moving forward with clinical trials in this devastating disease. Although JNCL is a rare disease, our research has implications that can be generalized to the study of other degenerative neurologic disorders in children and for preparing translational clinical trials in these diseases.

神经元蜡样脂褐质沉积症（NCL，Batten 病）是遗传性常染色体隐性溶酶体贮积病。尽管 NCL 相对罕见，但儿童期变体代表了儿童期最常见的神经退行性疾病，在美国影响的人数约为 1:25,000，在全球范围内的发病率高达 1:12,500。 NCL 变体的主要区别在于其不同的发病年龄和症状进展速度。由于 CLN-3 突变，青少年 NCL (JNCL) 是 NCL 的更常见形式之一。 JNCL 的症状在 5 至 8 岁之间出现，进展缓慢，直至在 2 岁或 3 岁的时候死亡。 JNCL 最常见的早期症状是视力丧失、癫痫发作性痴呆、行为困难和运动技能受损。随着疾病的进展，孩子变得越来越残疾，并且照顾者负担沉重。 关于 JNCL 自然史的定量数据很少。众所周知，JNCL 包括广泛的 一系列神经、神经心理学和行为/精神症状。随着疾病的进展，言语、语言、运动技能和自我护理技能逐渐丧失。在某些个体中，攻击性行为、焦虑、幻觉、强迫观念或性格变化很突出。然而，尚不清楚每种症状对整体残疾和护理人员负担的影响程度。也不知道癫痫发作和癫痫控制在多大程度上导致残疾。 此外，尚不清楚基因型在多大程度上影响表型变异。 我们提出了三个具体目标，即定量确定 JNCL 的自然史，表征 JNCL 的神经心理学和行为表型，建立 JNCL 评级量表的有效性和可靠性，并确定个体 JNCL 受试者的表型和基因型之间的相关性。 该项目的成功完成将为推进这种毁灭性疾病的临床试验提供必要的框架。尽管 JNCL 是一种罕见疾病，但我们的研究具有一定的意义，可以推广到儿童其他退行性神经系统疾病的研究以及准备这些疾病的转化临床试验。