DELINEATION OF THE PHENOTYPE IN CARRIERS OF NIEMANN PICK DISEASE TYPES A & B

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 A型和B型尼曼-匹克病（NPD）是由鞘磷脂酶（ASM）缺乏引起的溶酶体贮积症。 A型NPD是一种严重的神经病理性疾病，通常会导致三岁以下的死亡。 相比之下，B型NPD患者很少或没有神经系统受累，并且通常存活到青春期后期或成年期。 以总胆固醇和LDL胆固醇升高以及HDL胆固醇降低为特征的血脂异常是该疾病表型的一致特征。 初步数据表明，这种疾病的一些专性载体也显示这种疾病的表现。 因此，本提案的具体目标是：（1）确定酸性鞘磷脂酶缺乏症的专性携带者的脂质谱;（2）在专性携带者中进行结构化调查，以收集关于其大家庭成员中存在心血管疾病的详细信息;（3）从具有成为携带者的遗传风险的家庭成员中收集DNA样本，并确定其携带者状态和脂质谱;以及（4）进行研究以确定专性携带者是否显示其他常见疾病表现，例如器官肿大和肺浸润。

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 lysosomal storage disorders resulting from the deficiency of sphinogomyelinase (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. Dyslipidemia characterized by elevated total and LDL cholesterol and decresased HDL cholesterol is a consistent feature of the phenotype in this disorder. Preliminary data suggests that some obligate carriers of this disorder also display this disease manifestation. Thus, the specific aims of this proposal are to: (1) determine the lipid profiles in obligate carriers of acid sphingomyelinase deficiency; (2) carry out a structured survey in obligate carriers to collect detailed information about the presence of cardiovascular disease in their extended family members; (3) collect DNA samples from family members at genetic risk of being carriers and determine their carrier status and lipid profiles; and (4) conduct studies to determine if obligate carriers display other common disease manifestation such as organomegaly and pulmonary infiltration.