Investigations of Methylmalonic Acidemia and Related Dis

这项研究包括遗传性甲基丙二酸血症(MMA)和钴胺缺乏症。这些代谢紊乱在遗传上是不同的，共同代表了有机酸血症的一个重要子集。我们通过翻译的方法研究遗传性甲基丙二酸血症和钴缺乏障碍，包括对受影响的患者进行临床和代谢评估，并使用动物模型在实验室检查这些障碍。我们回顾了文献1中的方法。我们已经建立了甲基丙二酸血症的小鼠和蠕虫模型，并在过去的一年中描述了这两个系统的特征。这项研究的总体目标是定义患者身上出现的并发症，在小鼠或其他生物身上复制发现，并使用组合信息来指导新疗法的开发和测试，如基因疗法和干细胞疗法。我们维持一个小鼠群体，使用细胞培养设施，用放射性同位素进行实验来研究细胞内的新陈代谢，并在实验室里培养小蛔虫。 人类主题研究的重点是评估美国甲基丙二酸血症的自然历史，以进一步了解这一组疾病的治疗、结果和并发症。自去年以来，我们已经开发了一个结果研究的患者数据库，并招募了40名参与者参与我们的临床研究研究。我们研究了实体器官移植对MMA的影响，描述了患有疾病相关中风的患者中的一种新的神经综合征，并描述了在一组患者中看到的一系列眼部表现。患者通常作为住院患者在NIH临床研究中心住院3至4天，并接受广泛的代谢测试。许多成年人需要对中枢神经系统进行磁共振成像和磁共振波谱检查。我们使用高场强磁铁(3Telsa)进行这些研究。

This research study encompasses the hereditary methylmalonic acidemias (MMA) and cobalamin deficiency disorders. These metabolic disorders are genetically heterogeneous and collectively represent an important subset of the organic acidemias. They disorders are reviewed in references 2 through 4. We study the hereditary methylmalonic acidemias and cobalmin deficiency disorders via a translational approach that includes a clinical and metabolic evaluation of affected patients and the use animal models to examine the disorder in the laboratory. We review our approaches in reference 1. We have developed mouse and worm models of methylmalonic acidemia and have characterized both systems in the past year. The general goal of the research is to define the complications seen in the patients, replicate the findings in mice or other organisms and use the combined information to guide the development and testing of new therapies, such as gene and stem cell therapy. We maintain a mouse colony, use cell culture facilities, perform experiments with radioactive isotopes to study metabolism in cells and grow small roundworms in the laboratory. The human subject research is focused on assessing the natural history of methylmalonic acidemia in the United States to further understand the treatment, outcome and complications in this group of disorders. We have developed a patient database for outcomes research and have enrolled 40 participants in our clinical research studies since last year. We have studied the effects of solid organ transplantation on MMA, delineated a new neurologic syndrome in pateints who have suffered from a disease-related stroke and decribed a range of eye findings seen in one subset of patients. The patients are usually admitted to the NIH Clinical Research Center as inpatients for 3 to 4 days and undergo extensive metabolic testing. Many adults need magnetic resonance imaging and magnetic resonance spectroscopy of the central nervous system. We use a high field strength magnet ( 3 Telsa) for these studies.