Clinical and Neuropsychological Investigations in Batten Disease

巴顿病的临床和神经心理学研究

• 批准号: 7472347
• 负责人: JONATHAN W. MINK
• 金额: $ 30.8万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7472347
• 关键词: Activities of Daily Living; Adolescent; Affect; Age; Age of Onset; Aggressive behavior; Anxiety; Behavior; Behavior Disorders; Behavioral; Biology; Blindness; Caregiver Burden; Cessation of life; Child; Childhood; Clinical; Clinical Trials; Data; Dementia; Development; Diagnosis; Diagnostic; Disabled Persons; Disease; Emotional; Family; Future; Genetic; Genotype; Hallucinations; Impact Seizures; Impaired cognition; Impairment; Incidence; Individual; Inherited; Intervention; Investigation; Knowledge; Laboratories; Language; Life; Lysosomal Storage Diseases; Manuals; Mink; Modeling; Molecular; Motor; Motor Skills; Mutation; Natural History; Neurodegenerative Disorders; Neurologic; Neurologic Manifestations; Neuronal Ceroid-Lipofuscinosis; Obsession; Outcome; Outcome Measure; Palliative Care; Patients; Personality; Phenotype; Physical assessment; Prevalence; Range; Rare Diseases; Rate; Research; Research Personnel; Seizures; Self Care; Severities; Speech; Spielmeyer-Vogt Disease; Staging; Symptoms; Therapeutic; Therapeutic Intervention; Therapy Clinical Trials; Time; Training; Translational Research; Universities; Validation; Validity and Reliability; Variant; Work; base; disability; impression; motor disorder; neurobehavioral; neuropsychological; novel therapeutics; programs; skills; symptom management; translational clinical trial

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：神经性蜡样脂褐质病（NCLs， Batten病）是一种遗传性常染色体隐性溶酶体贮积病。虽然nclc相对罕见，但儿童变异代表了最常见的儿童神经退行性疾病，在美国的发病率约为1:25,000，全球发病率高达1:12,500。NCL变体的区别主要在于发病年龄和症状进展速度的不同。由于CLN-3突变，幼年型NCL （JNCL）是一种更常见的NCL形式。JNCL的症状发作在5至8岁之间，进展缓慢，直到生命的第二或第三个十年死亡。JNCL最常见的早期症状是视力丧失、癫痫性痴呆、行为困难和运动技能受损。随着疾病的发展，儿童的残疾程度日益加重，照料者的负担也越来越重。目前关于JNCL自然历史的定量资料很少。众所周知，JNCL包括广泛的神经学、神经心理学和行为/精神症状。随着病情的发展，患者会逐渐丧失言语、语言、运动技能和自理能力。在一些个体中，攻击行为、焦虑、幻觉、强迫症或人格改变是突出的。然而，目前尚不清楚每种症状在多大程度上导致整体残疾和照顾者负担。目前还不清楚癫痫发作和癫痫控制在多大程度上导致残疾。此外，基因型对表型变异的影响程度尚不清楚。我们提出了三个具体目标：定量确定JNCL的自然史，表征JNCL的神经心理和行为表型，建立JNCL评分量表的效度和信度，以及确定JNCL个体受试者的表型和基因型之间的相关性。这一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，但我们的研究可以推广到其他儿童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。