title: Challenges for basic research in glutaryl-CoA dehydrogenase deficiency.
abstract: During the last decades, efforts have been made to elucidate the complex mechanisms underlying neuronal damage in glutaryl-CoA dehydrogenase deficiency. A combination of in vitro and in vivo investigations have facilitated the development of several hypotheses, including the probable pathogenic role of accumulating glutaric acid and 3-hydroxyglutaric acid. However, there are still many shortcomings that limit an evidence-based approach to treating this inborn error of metabolism. Major future goals should include generation of a suitable animal model for acute striatal necrosis, investigation of the formation, distribution and exact intra- and extracellular concentrations of accumulating metabolites, a deeper understanding of striatal vulnerability, and systematic investigation of effects on cerebral gene expression during development and of the modulatory role of inflammatory cytokines.
authors.affiliation: Department of General Pediatrics, Division of Metabolic and Endocrine Diseases, University Children's Hospital Heidelberg, D-69120 Heidelberg, Germany. stefan_koelker@med.uni-heidelberg.de
authors.forename: S
authors.initials: S
authors.lastname: Kölker
authors.forename: K A
authors.initials: KA
authors.lastname: Strauss
authors.forename: S I
authors.initials: SI
authors.lastname: Goodman
authors.forename: G F
authors.initials: GF
authors.lastname: Hoffmann
authors.forename: J G
authors.initials: JG
authors.lastname: Okun
authors.forename: D M
authors.initials: DM
authors.lastname: Koeller
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000473:pathology* / Q000628:therapy; D000818:Animals; D005977:Glutarates / Q000378:metabolism; D050770:Glutaryl-CoA Dehydrogenase; D006801:Humans; D017072:Neostriatum / Q000473:pathology; D009474:Neurons / Q000473:pathology; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000172:deficiency*
chemical_list: C108959:3-hydroxyglutaric acid; D005977:Glutarates; D044925:Oxidoreductases Acting on CH-CH Group Donors; D050770:Glutaryl-CoA Dehydrogenase; C035736:glutaric acid