Are NCLs atypical in Latin America? Phenotypic and Genotypic analyses.

描述(申请人提供)：神经性干酪样脂褐质沉着症(NCL)可能是最常见的进行性遗传性神经退行性疾病，起病于儿童期。它们可以在所有年龄开始，进展的特征是以下一种或多种症状：视力衰竭、癫痫发作、精神和运动退化。结果是致命的，治疗是对症和姑息的。我们提供的初步数据表明，NCLS在南美被低估了诊断。我们将与罗切斯特大学的巴顿疾病诊断和临床研究中心(BDDCRC)合作。这一应用程序的最初目的是建立和改进南美洲现有的NCLS诊断技术。此外，通过我们的合作，我们还将完善我们对南美NCLS的临床特征、进展和基因与表型相关性的理解。最后，我们将建立确定监测临床状态的二级生物标志物的基础，以改进对疾病进展的监测，并应用于治疗策略。我们提出了以下具体目标：1)NCL诊断工具的开发。2.)南美NCLS的基因型与表型相关性。3.)NCLS生物标志物的研究进展最近的进展极大地扩展了关于NCLS的遗传学和生物学知识。这些进展为NCL的实验治疗提供了基础。开发新的治疗干预措施的必要性很大；目前的治疗在可能的情况下仅限于症状管理，并转向对终末期疾病的姑息治疗。在严格评估新的干预措施之前，必须获得定量的自然历史数据，并制定有效、可靠的结果衡量标准。公共卫生相关性：目前的翻译调查将在诊断为NCLS南美洲的情况下克服。受影响的患者及其家人将从诊断和预后中受益，并可采取适当的护理措施。此外，独特的种群将允许对适用于南美洲处于风险中的NCL家庭的详细研究，并在全球范围内更好地了解NCLS中所证明的遗传和生化多样性。

DESCRIPTION (provided by applicant): The Neuronal Ceroid Lipofuscinoses (NCL) is probably the most frequent group of progressive inherited neurodegenerative diseases with childhood onset. They can start at all ages and progression is characterized by one or more of the following symptoms: vision failure, seizures, mental and motor regression. The outcome is fatal with therapies being symptomatic and palliative. We present preliminary data indicating that NCLs are under diagnosed in South America. We will collaborate with the Batten Disease Diagnostic and Clinical Research Center (BDDCRC) at the University of Rochester. The initial aim of this application is to establish and improve upon existing technologies for diagnosis of NCLs in South America. In addition, through our collaboration we will also refine our understanding of the clinical characteristics, progression and genotype to phenotype correlations for NCLs in South America. Finally, we will establish the basis for identifying secondary Biomarkers for monitoring clinical status for improved monitoring of disease progression for application of treatment strategies. We propose the following specific aims: 1.) Development of NCL Diagnostic Tools. 2.) Genotype to Phenotype Correlation for South American NCLs. 3.) Development of Biomarkers for NCLs. Recent advances have greatly expanded knowledge of genetics and biology of the NCLs. These advances have provided the basis for experimental therapeutics in NCL. The need for development of new therapeutic interventions is great; current treatment is limited to symptom management when possible, with a shift to palliative care for end-stage disease. Before new interventions can be evaluated rigorously, quantitative natural history data must be obtained and a valid, reliable outcome measure must be developed. PUBLIC HEALTH RELEVANCE: The present translational investigation will overcome under diagnosis of NCLs South America. Affected patients and their families will benefit from diagnosis and prognosis and appropriate care can be followed. Moreover, the unique population will allow for detailed research applicable to the NCL families at risk in S. America and development of a greater global understanding of the genetic and biochemical diversity evidenced in the NCLs.