Excitotoxicity and bioenergetics in glutaryl-CoA dehydrogenase deficiency

Stefan Kölker, David Koeller, S. Sauer, F. Hörster, M. A. Schwab, G. F. Hoffmann, K. Ullrich, J. G. Okun

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Glutaryl-CoA dehydrogenase deficiency is an inherited organic acid disorder with predominantly neurological presentation. The biochemical hallmark of this disease is an accumulation and enhanced urinary excretion of two key organic acids, glutaric acid and 3-hydroxyglutaric acid. If untreated, acute striatal damage is often precipitated by febrile illnesses during a vulnerable period of brain development in infancy or early childhood, resulting in a dystonic dyskinetic movement disorder. 3-Hydroxyglutaric and glutaric acids are structurally similar to glutamate, the main excitatory amino acid of the human brain, and are considered to play an important role in the pathophysiology of this disease. 3-Hydroxyglutaric acid induces excitotoxic cell damage specifically via activation of N-methyl-D-aspartate receptors. It has also been suggested that secondary amplification loops potentiate the neurotoxic properties of these organic acids. Probable mechanisms for this effect include cytokine-stimulated NO production, a decrease in energy metabolism, and reduction of cellular creatine phosphate levels. Finally, maturation-dependent changes in the expression of neuronal glutamate receptors may affect the vulnerability of the immature brain to excitotoxic cell damage in this disease.

Original languageEnglish (US)
Pages (from-to)805-812
Number of pages8
JournalJournal of Inherited Metabolic Disease
Volume27
Issue number6
DOIs
StatePublished - 2004

Fingerprint

Energy Metabolism
Acids
Brain
Corpus Striatum
Excitatory Amino Acids
Phosphocreatine
Movement Disorders
Glutamate Receptors
N-Methyl-D-Aspartate Receptors
Glutamic Acid
Fever
Cytokines
Glutaric Acidemia I
3-hydroxyglutaric acid
glutaric acid

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics
  • Endocrinology

Cite this

Excitotoxicity and bioenergetics in glutaryl-CoA dehydrogenase deficiency. / Kölker, Stefan; Koeller, David; Sauer, S.; Hörster, F.; Schwab, M. A.; Hoffmann, G. F.; Ullrich, K.; Okun, J. G.

In: Journal of Inherited Metabolic Disease, Vol. 27, No. 6, 2004, p. 805-812.

Research output: Contribution to journalArticle

Kölker, S, Koeller, D, Sauer, S, Hörster, F, Schwab, MA, Hoffmann, GF, Ullrich, K & Okun, JG 2004, 'Excitotoxicity and bioenergetics in glutaryl-CoA dehydrogenase deficiency', Journal of Inherited Metabolic Disease, vol. 27, no. 6, pp. 805-812. https://doi.org/10.1023/B:BOLI.0000045762.37248.28
Kölker, Stefan ; Koeller, David ; Sauer, S. ; Hörster, F. ; Schwab, M. A. ; Hoffmann, G. F. ; Ullrich, K. ; Okun, J. G. / Excitotoxicity and bioenergetics in glutaryl-CoA dehydrogenase deficiency. In: Journal of Inherited Metabolic Disease. 2004 ; Vol. 27, No. 6. pp. 805-812.
@article{fbadc932d14a41ae95eccabad5c94776,
title = "Excitotoxicity and bioenergetics in glutaryl-CoA dehydrogenase deficiency",
abstract = "Glutaryl-CoA dehydrogenase deficiency is an inherited organic acid disorder with predominantly neurological presentation. The biochemical hallmark of this disease is an accumulation and enhanced urinary excretion of two key organic acids, glutaric acid and 3-hydroxyglutaric acid. If untreated, acute striatal damage is often precipitated by febrile illnesses during a vulnerable period of brain development in infancy or early childhood, resulting in a dystonic dyskinetic movement disorder. 3-Hydroxyglutaric and glutaric acids are structurally similar to glutamate, the main excitatory amino acid of the human brain, and are considered to play an important role in the pathophysiology of this disease. 3-Hydroxyglutaric acid induces excitotoxic cell damage specifically via activation of N-methyl-D-aspartate receptors. It has also been suggested that secondary amplification loops potentiate the neurotoxic properties of these organic acids. Probable mechanisms for this effect include cytokine-stimulated NO production, a decrease in energy metabolism, and reduction of cellular creatine phosphate levels. Finally, maturation-dependent changes in the expression of neuronal glutamate receptors may affect the vulnerability of the immature brain to excitotoxic cell damage in this disease.",
author = "Stefan K{\"o}lker and David Koeller and S. Sauer and F. H{\"o}rster and Schwab, {M. A.} and Hoffmann, {G. F.} and K. Ullrich and Okun, {J. G.}",
year = "2004",
doi = "10.1023/B:BOLI.0000045762.37248.28",
language = "English (US)",
volume = "27",
pages = "805--812",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer Netherlands",
number = "6",

}

TY - JOUR

T1 - Excitotoxicity and bioenergetics in glutaryl-CoA dehydrogenase deficiency

AU - Kölker, Stefan

AU - Koeller, David

AU - Sauer, S.

AU - Hörster, F.

AU - Schwab, M. A.

AU - Hoffmann, G. F.

AU - Ullrich, K.

AU - Okun, J. G.

PY - 2004

Y1 - 2004

N2 - Glutaryl-CoA dehydrogenase deficiency is an inherited organic acid disorder with predominantly neurological presentation. The biochemical hallmark of this disease is an accumulation and enhanced urinary excretion of two key organic acids, glutaric acid and 3-hydroxyglutaric acid. If untreated, acute striatal damage is often precipitated by febrile illnesses during a vulnerable period of brain development in infancy or early childhood, resulting in a dystonic dyskinetic movement disorder. 3-Hydroxyglutaric and glutaric acids are structurally similar to glutamate, the main excitatory amino acid of the human brain, and are considered to play an important role in the pathophysiology of this disease. 3-Hydroxyglutaric acid induces excitotoxic cell damage specifically via activation of N-methyl-D-aspartate receptors. It has also been suggested that secondary amplification loops potentiate the neurotoxic properties of these organic acids. Probable mechanisms for this effect include cytokine-stimulated NO production, a decrease in energy metabolism, and reduction of cellular creatine phosphate levels. Finally, maturation-dependent changes in the expression of neuronal glutamate receptors may affect the vulnerability of the immature brain to excitotoxic cell damage in this disease.

AB - Glutaryl-CoA dehydrogenase deficiency is an inherited organic acid disorder with predominantly neurological presentation. The biochemical hallmark of this disease is an accumulation and enhanced urinary excretion of two key organic acids, glutaric acid and 3-hydroxyglutaric acid. If untreated, acute striatal damage is often precipitated by febrile illnesses during a vulnerable period of brain development in infancy or early childhood, resulting in a dystonic dyskinetic movement disorder. 3-Hydroxyglutaric and glutaric acids are structurally similar to glutamate, the main excitatory amino acid of the human brain, and are considered to play an important role in the pathophysiology of this disease. 3-Hydroxyglutaric acid induces excitotoxic cell damage specifically via activation of N-methyl-D-aspartate receptors. It has also been suggested that secondary amplification loops potentiate the neurotoxic properties of these organic acids. Probable mechanisms for this effect include cytokine-stimulated NO production, a decrease in energy metabolism, and reduction of cellular creatine phosphate levels. Finally, maturation-dependent changes in the expression of neuronal glutamate receptors may affect the vulnerability of the immature brain to excitotoxic cell damage in this disease.

UR - http://www.scopus.com/inward/record.url?scp=7244221531&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7244221531&partnerID=8YFLogxK

U2 - 10.1023/B:BOLI.0000045762.37248.28

DO - 10.1023/B:BOLI.0000045762.37248.28

M3 - Article

C2 - 15505385

AN - SCOPUS:7244221531

VL - 27

SP - 805

EP - 812

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

SN - 0141-8955

IS - 6

ER -