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

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 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.