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Challenges for basic research in glutaryl-CoA dehydrogenase deficiency

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Journal of Inherited Metabolic Disease

Abstract

Summary: 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.

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Authors and Affiliations

  1. Department of General Pediatrics, Division of Metabolic and Endocrine Diseases, University Children's Hospital Heidelberg, Germany

    S. KÖlker, G. F. Hoffmann & J. G. Okun

  2. Clinic for Special Children, Strasburg, Pennsyvania, USA

    K. A. Strauss

  3. Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado, USA

    S. I. Goodman

  4. Departments of Pediatrics and Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon, USA

    D. M. Koeller

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  1. S. KÖlker
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  2. K. A. Strauss
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  3. S. I. Goodman
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  4. G. F. Hoffmann
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  5. J. G. Okun
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  6. D. M. Koeller
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Correspondence to S. KÖlker.

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KÖlker, S., Strauss, K.A., Goodman, S.I. et al. Challenges for basic research in glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis 27, 843–849 (2004). https://doi.org/10.1023/B:BOLI.0000045768.38073.22

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  • DOI: https://doi.org/10.1023/B:BOLI.0000045768.38073.22

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