Abstract

This research study encompasses the hereditary methylmalonic acidemias and cobalmin deficiency disorders. These metabolic disorders are genetically heterogeneous and collectively represent an important subset of the organic acidemias. 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 use animal models to examine the disorder in the laboratory. We have developed mouse and worm models of methylmalonic acidemia. 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.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Intramural Research (Z01)
Project #
1Z01HG200318-01
Application #
6989007
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2004
Total Cost
Indirect Cost

  Institution

Name
Human Genome Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Pena, Loren; Franks, Jill; Chapman, Kimberly A et al. (2012) Natural history of propionic acidemia. Mol Genet Metab 105:5-9
Schreiber, John; Chapman, Kimberly A; Summar, Marshall L et al. (2012) Neurologic considerations in propionic acidemia. Mol Genet Metab 105:10-5
Bassim, C W; Wright, J T; Guadagnini, J P et al. (2009) Enamel defects and salivary methylmalonate in methylmalonic acidemia. Oral Dis 15:196-205
Chandler, Randy J; Sloan, Jennifer; Fu, Hong et al. (2007) Metabolic phenotype of methylmalonic acidemia in mice and humans: the role of skeletal muscle. BMC Med Genet 8:64
Chandler, Randy J; Tsai, Matthew S; Dorko, Kenneth et al. (2007) Adenoviral-mediated correction of methylmalonyl-CoA mutase deficiency in murine fibroblasts and human hepatocytes. BMC Med Genet 8:24
Chandler, Randy J; Aswani, Vijay; Tsai, Matthew S et al. (2006) Propionyl-CoA and adenosylcobalamin metabolism in Caenorhabditis elegans: evidence for a role of methylmalonyl-CoA epimerase in intermediary metabolism. Mol Genet Metab 89:64-73
Chandler, R J; Venditti, C P (2005) Genetic and genomic systems to study methylmalonic acidemia. Mol Genet Metab 86:34-43
Venditti, C P; Harris, M C; Huff, D et al. (2004) Congenital cardiomyopathy and pulmonary hypertension: another fatal variant of cytochrome-c oxidase deficiency. J Inherit Metab Dis 27:735-9
Venditti, Charles P; Hunt, Piper; Donnenfeld, Alan et al. (2004) Mosaic paternal uniparental (iso)disomy for chromosome 20 associated with multiple anomalies. Am J Med Genet A 124A:274-9