Defects of pyruvate metabolism and the Krebs cycle.

[pyruvate dehydrogenase deficiency]

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 E 1 alpha owing to the mutation in the subunit E 1 alpha 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 .