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.

神经元蜡样质脂褐质沉积症（NCL，Batten病）是遗传的、常染色体隐性的溶酶体贮积病。虽然NCL相对罕见，但儿童期变异是儿童期最常见的神经退行性疾病，在美国影响约1：25，000，在全球范围内的发病率高达1：12，500。NCL变体主要通过其不同的发病年龄和症状进展的速率来区分。由于CLN-3突变引起的幼年NCL（JNCL）是NCL的常见形式之一。JNCL的症状发作在5至8岁之间，缓慢进展，直至在生命的第二或第三个十年中死亡。JNCL最常见的早期症状是视力丧失、癫痫痴呆、行为困难和运动技能受损。随着疾病的发展，儿童的残疾程度越来越严重，照顾者的负担也越来越重。 关于JNCL的自然历史的定量数据很少。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会逐渐丧失。在某些个体中，攻击性行为，焦虑，幻觉，强迫症或人格改变是突出的。然而，目前尚不清楚每种类型的症状在多大程度上导致整体残疾和照顾者负担。也不知道癫痫发作和控制癫痫发作在多大程度上会导致残疾。 此外，基因型在多大程度上影响表型变异性尚不清楚。 我们提出了三个具体的目标，以确定JNCL的自然史定量，表征JNCL的神经心理和行为表型，建立有效性和可靠性的评级量表为JNCL，并确定表型和基因型之间的相关性个别JNCL科目。 该项目的成功完成将为推进这一毁灭性疾病的临床试验提供必要的框架。虽然JNCL是一种罕见的疾病，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，并为这些疾病的转化临床试验做准备。