title: Defects of pyruvate metabolism and the Krebs cycle.
abstract: Seizures and metabolic disease are frequently associated, either indirectly as a consequence of the metabolically caused brain dysgenesis or directly by the metabolic derangement. This article describes defects in pyruvate metabolism (pyruvate carboxylase deficiency, pyruvate dehydrogenase deficiency) and Krebs cycle defects such as fumarase deficiency. Clinical characterizations and diagnostic strategies have been developed for each of these diseases. In contrast, very little is known about the specific epileptic features in these disorders. In females with a pyruvate dehydrogenase deficiency E1alpha owing to the mutation in the subunit E1alpha of the pyruvate dehydrogenase complex West's syndrome associated with large ventricles and corpus callosum agenesis on magnetic resonance imaging can be the main feature of the disease. In fumarase deficiency, prenatal brain dysgenesis is the most prominent feature of the disease. Diagnosis of these disorders requires measurements of lactate and pyruvate in plasma and cerebrospinal fluid, analysis of amino acids in plasma and organic acids in urine, and neuroradiologic investigations. Further biochemical and molecular analysis leads to a definitive diagnosis and opens the way to adequate treatment, genetic counseling, and prenatal diagnosis.
authors.affiliation: Department of Pediatric Neurology, Free University of Brussels, Flemish speaking, Brussels, Belgium. linda.demeirleir@az.vub.ac.be
authors.forename: Linda
authors.initials: L
authors.lastname: De Meirleir
mesh_terms: D001921:Brain / Q000002:abnormalities*; D002952:Citric Acid Cycle / Q000502:physiology*; D003937:Diagnosis, Differential; D005649:Fumarate Hydratase / Q000172:deficiency*; D006801:Humans; D008279:Magnetic Resonance Imaging; D015324:Pyruvate Carboxylase Deficiency Disease / Q000150:complications / Q000175:diagnosis*; D015325:Pyruvate Dehydrogenase Complex Deficiency Disease / Q000150:complications / Q000175:diagnosis* / Q000178:diet therapy; D019289:Pyruvic Acid / Q000378:metabolism*; D012640:Seizures / Q000209:etiology; D012737:Sex Factors
chemical_list: D019289:Pyruvic Acid; D005649:Fumarate Hydratase