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

点击翻译按钮获取中文摘要

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.