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; 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.

神经元粘膜脂蛋白酶（NCLS，Batten疾病）是遗传的，常染色体隐性溶酶体储存疾病。尽管NCL相对较少，但童年的变体代表了童年的最常见的神经退行性疾病，在美国影响约1：25,000，并且在全球范围内发病高达1：12,500。 NCL变体主要是由它们不同年龄的发作年龄和症状进展的速度来区分。由于CLN-3突变，少年NCL（JNCL）是NCL的最常见形式之一。 JNCL的症状发作在5至8岁之间，其进展缓慢，直到生命的第二十年或第三个十年死亡。 JNCL最常见的早期症状是视力丧失，癫痫发作痴呆，行为困难和运动技能受损。随着疾病的发展，孩子变得越来越残疾，并且有很大的照顾者负担。 关于JNCL自然史的数量数据很少。众所周知，JNCL包括一个广泛的 神经系统，神经心理学和行为/精神病症状的范围。随着疾病的发展，语音，语言，运动技能和自我保健技能的逐渐丧失。在某些人中，侵略性行为，焦虑，幻觉，痴迷或人格变化是突出的。但是，每种类型的症状在多大程度上导致整体残疾和护理人员负担，尚不清楚。还不知道癫痫发作和癫痫发作控制的程度有助于残疾。 此外，尚不清楚基因型在多大程度上影响表型变异性。 我们提出了三个特定的目的，以定量确定JNCL的自然历史，以表征JNCL的神经心理学和行为表型，以确定JNCL评级量表的有效性和可靠性，并确定单个JNCL受试者表型和基因型之间的相关性。 该项目的成功完成将提供必要的框架，以进行这种毁灭性疾病的临床试验。尽管JNCL是一种罕见的疾病，但我们的研究具有可以推广到儿童中其他退化性神经系统疾病的研究，并准备这些疾病中的转化临床试验。