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

描述（由申请人提供）：神经元蜡样脂褐质病（NCL）可能是最常见的儿童期发作的进行性遗传性神经退行性疾病。它们可以在所有年龄开始，并且进展的特征是以下症状中的一个或多个：视力衰竭，癫痫发作，精神和运动退化。结果是致命的，治疗是对症的和姑息的。我们目前的初步数据表明，NCL在南美洲的诊断不足。我们将与罗切斯特大学的巴顿病诊断和临床研究中心（BDDCRC）合作。本申请的最初目的是建立和改进南美NCL诊断的现有技术。此外，通过我们的合作，我们还将完善我们对南美NCL的临床特征，进展和基因型与表型相关性的理解。最后，我们将为确定用于监测临床状态的次要生物标志物建立基础，以改善对疾病进展的监测，从而应用治疗策略。我们提出以下具体目标：1.）NCL诊断工具的开发。2.）的情况。南美NCL的基因型与表型相关性。3.）第三章NCL的生物标志物的开发。最近的进展极大地扩展了NCL的遗传学和生物学知识。这些进展为NCL的实验性治疗提供了基础。开发新的治疗干预措施的必要性很大;目前的治疗仅限于症状管理，如果可能的话，对终末期疾病转向姑息治疗。在对新的干预措施进行严格评估之前，必须获得定量的自然史数据，并制定有效、可靠的结果衡量标准。公共卫生相关性：目前的翻译研究将克服南美NCL的诊断不足。受影响的患者及其家属将受益于诊断和预后，并可以采取适当的护理。此外，独特的人口将允许详细的研究适用于NCL家庭的风险在S。美国和发展的遗传和生物化学多样性的更大的全球性的理解证明在NCL。

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.