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Glutaryl-CoA Dehydrogenase Deficiency: Region-Specific Analysis of Organic Acids and Acylcarnitines in post mortem Brain Predicts Vulnerability of the Putamen

Lookup NU author(s): Dr Morteza Pourfarzam


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The neurometabolic disorder glutaryl-CoA dehydrogenase (GCDH) deficiency is biochemically characterised by an accumulation of the marker metabolites 3-hydroxyglutaric acid, glutaric acid, and glutarylcarnitine. If untreated, the disease is complicated by acute encephalopathic crises, resulting in neurodegeneration of vulnerable brain regions, in particular the putamen. 3-Hydroxyglutaric acid is considered the major neurotoxin in this disease. There are only preliminary data concerning glutaric acid concentrations in the brains of affected children and the distribution of 3-hydroxyglutaric acid and glutarylcarnitine has not been described. In the present study, we investigated post mortem the distribution of 3-hydroxyglutaric and glutaric acids as well as glutarylcamitine in 14 different brain regions, internal organs, and body fluids (urine, plasma, cerebrospinal fluid) in a 14-year-old boy. 3-Hydroxyglutaric acid showed the highest concentration (62 nmol/g protein) in the putamen among all brain areas investigated. The glutarylcarnitine concentration was also highest in the putamen (7.1 nmol/g protein). We suggest that the regional-specific differences in the relative concentrations of 3-hydroxyglutaric acid contribute to the pattern of neuronal damage in this disease. These results provide an explanatory basis for the high vulnerability of the putamen in this disease, adding to the strong corticostriatal glutamatergic input into the putamen and the high excitotoxic susceptibility of neostriatal medium spiny neurons.

Publication metadata

Author(s): Kolker S, Hoffmann GF, Schor DSM, Feyh P, Wagner L, Jeffrey I, Pourfarzam M, Okun JG, Zschocke J, Baric I, Bain MD, Jakobs C, Chalmers RA

Publication type: Article

Publication status: Published

Journal: Neuropediatrics

Year: 2003

Volume: 34

Issue: 5

Pages: 253-260

ISSN (print): 0174-304X

ISSN (electronic): 1439-1899

Publisher: Georg Thieme Verlag


DOI: 10.1055/s-2003-43261

PubMed id: 14598231


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