Pyruvate dehydrogenase deficiency and epilepsy.

[pyruvate dehydrogenase deficiency]

The pyruvate dehydrogenase complex (PDHc ) is a mitochondrial matrix multienzyme complex that provides the link between glycolysis and the tricarboxylic acid (TCA ) cycle by catalyzing the conversion of pyruvate into acetyl-CoA . PDHc deficiency is one of the commoner metabolic disorders of lactic acidosis presenting with neurological phenotypes that vary with age and gender . In this mini-review , we postulate mechanisms of epilepsy in the setting of PDHc deficiency using two illustrative cases (one with pyruvate dehydrogenase complex E 1 -alpha polypeptide (PDHA 1 ) deficiency and the second one with pyruvate dehydrogenase complex E 1 -beta subunit (PDHB ) deficiency (a rare subtype of PDHc deficiency )) and a selected review of published case series . PDHc plays a critical role in the pathway of carbohydrate metabolism and energy production . In severe deficiency states the resulting energy deficit impacts on brain development in utero resulting in structural brain anomalies and epilepsy . Milder deficiency states present with variable manifestations that include cognitive delay , ataxia , and seizures . Epileptogenesis in PDHc deficiency is linked to energy failure , development of structural brain anomalies and abnormal neurotransmitter metabolism . The use of the ketogenic diet bypasses the metabolic block , by providing a direct source of acetyl-CoA , leading to amelioration of some symptoms . Genetic counseling is essential as PDHA 1 deficiency (commonest defect ) is X-linked although females can be affected due to unfavorable lyonization , while PDHB and PDH phosphatase (PDP ) deficiencies (much rarer defects ) are of autosomal recessive inheritance . Research is in progress for looking into animal models to better understand pathogenesis and management of this challenging disorder .

Diseases
Validation

Diseases presenting "mitochondrial matrix multienzyme" symptom

pyruvate dehydrogenase deficiency

You can validate or delete this automatically detected symptom