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Neuropediatrics 2002; 33(5): 225-231
DOI: 10.1055/s-2002-36741
Review Article

Georg Thieme Verlag Stuttgart · New York

White Matter Disease in Cerebral Organic Acid Disorders: Clinical Implications and Suggested Pathomechanisms

S. Kölker 1 , E. Mayatepek 1 , G. F. Hoffmann 1
  • 1Department of General Pediatrics, Division of Metabolic and Endocrine Diseases, University Children's Hospital, Heidelberg, Germany
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Publikationsverlauf

Received: 11 April 2002

Accepted after Revision: 26 July 2002

Publikationsdatum:
21. Januar 2003 (online)

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Abstract

White matter abnormalities (including dys-, hypo-, demyelination and delayed myelation) are frequently found in cerebral organic acid disorders, a recently delineated subgroup of inherited organic acid disorders presenting predominantly with a neurological symptomatology. Biochemically, this disease subgroup lacks metabolic derangements, such as hypoglycemia, hyperammonemia and acidosis, and is characterized by an accumulation of organic acids that share structural similarities with the excitatory amino acid glutamate (D-2-, L-2-, 3-hydroxyglutarate, glutarate) or have been suggested as neurotransmitters/neuromodulators (N-acetylaspartylglutamate). Evidence from in vitro and in vivo studies is growing that relevant organic acids significantly contribute to the neuropathology of these diseases via interference with glutamatergic or GABAergic neurotransmission or impairment of energy metabolism. This article provides an overview on the clinical and neuroradiological presentation of white matter disease in cerebral organic acid disorders, focusing on the suggested pathomechanistic relevance of excitotoxicity, oxidative stress, and impaired energy metabolism.

Key words

Organic Acid Disorders - Myelination - Leukencephalopathy - Excitotoxicity - Glutamate Receptors - Reactive Oxygen Species

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Prof. Dr. Georg F. Hoffmann

Department of General Pediatrics
University Children's Hospital Heidelberg

Im Neuenheimer Feld 150

69120 Heidelberg

Germany

eMail: Georg_Hoffmann@med.uni-heidelberg.de