NIEMANN-PICK DISEASE: GENOTYPE/PHENOTYPE ANALYSES AND MOLECULAR BASED THERAPY

点击翻译按钮获取中文摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Types A and B Niemann-Pick disease (NPD) are storage disorders resulting from the deficiency of acid sphingomyelinase (ASM). Type A NPD is a severe neuronopathic disorder which uniformly leads to death by three years of age. In contrast, patients with Type B NPD have little or no neurologic involvement and often survive into late adolescence or adulthood. Despite the fact that this disorder was described over seventy years ago, no treatment is available for affected patients and no reliable biochemical tests have been developed to predict the phenotypic outcome of newly diagnosed individuals. Thus, the specific aims of this proposal are to: 1) characterize the natural history and spectrum of the phenotype in Type B disease in anticipation of a future clinical trial of enzyme replacement therapy (ERT) for this disorder, 2) identify causative ASM mutations, and 3) identify genotype/phenotype correlations.