ASSESSING NEURAL MECHANISMS OF INJURY IN INBORN ERRORS OF METABOLISM

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 尽管接受了治疗，但认知和运动障碍在患有影响蛋白质、碳水化合物和脂肪加工的遗传性新陈代谢障碍的个人中很常见。然而，这些缺陷在多大程度上涉及特定的认知或感觉运动领域尚不清楚。此外，对这些障碍中认知障碍的神经化学基础知之甚少。该项目将利用最先进的神经成像技术来研究先天代谢障碍中的认知和运动障碍，以检查可能解释这些缺陷的潜在神经基础。特别是，这项研究将解决患有先天性新陈代谢错误的个人以及杂合子疾病携带者在认知和生化方面的差异，他们可能会也可能不会表现出症状，这取决于遗传机制。这项研究将在乔治城大学的神经成像中心和GCRC进行。成像研究将得到分子和生化参数的补充。这些研究方法可以作为研究代谢性疾病中基因、生化标记物、脑功能和行为之间关系的模型。这项研究的结果应该有助于优化对患有先天性代谢错误的个人的护理和/或治疗，并有助于确定可用于监测治疗反应的疾病生物标志物。

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. Despite treatment, cognitive and motor deficits are common in individuals with inherited disorders of metabolism that affect processing of proteins, carbohydrates, and fats. However, the extent to which the deficits involve specific cognitive or sensorimotor domains is unknown. Furthermore, little is known about the neurochemical basis of cognitive impairment in these disorders. This project will investigate cognitive and motor dysfunction in inborn errors of metabolism utilizing state of the art neuroimaging to examine the underlying neural basis that may elucidate these defects. In particular, this study will address differences in cognition and biochemistry in individuals personally affected with inborn errors of metabolism, as well as heterozygous carriers of the disease, who may or may not manifest symptoms, depending upon the mechanism of inheritance. This study will be performed in the Neuroimaging center at Georgetown University, and GCRC . Imaging studies will be complemented with molecular and biochemical parameters. Such methods of investigation may serve as a model for studying the relationship between genes, biochemical markers, brain function, and behavior in metabolic diseases. The results of this study should help to optimize the care and/or treatment of individuals with inborn errors of metabolism, and serve to identify biomarkers of disease which can be used to monitor response to therapies.