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.
