ASSESSING NEURAL MECHANISMS OF INJURY IN INBORN ERRORS OF METABOLISM

这个子项目是许多利用 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来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 尽管进行了治疗，但认知和运动缺陷在患有影响蛋白质、碳水化合物和脂肪加工的遗传性代谢障碍的个体中很常见。 然而，缺陷涉及特定认知或感觉运动领域的程度尚不清楚。 此外，我们对这些疾病中认知障碍的神经化学基础知之甚少。 本计画将利用最先进的神经影像学技术，探讨先天性代谢缺陷的认知与运动功能障碍，以探讨可能阐明这些缺陷的潜在神经基础。特别是，这项研究将解决在认知和生物化学的差异，在个人影响与先天性代谢缺陷，以及杂合子携带者的疾病，谁可能会或可能不会表现出症状，这取决于遗传机制。 本研究将在乔治敦大学神经影像中心和GCRC进行。 影像学研究将补充分子和生化参数。 这种研究方法可以作为研究代谢性疾病中基因、生化标志物、脑功能和行为之间关系的模型。这项研究的结果应有助于优化护理和/或治疗的个人与先天性代谢缺陷，并有助于确定疾病的生物标志物，可用于监测治疗反应。

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.