Pyruvate Metabolism Disorders

Pyruvate is a substance formed in the processing of carbohydrates and proteins that serves as an energy source for cells. Problems with pyruvate metabolism can limit a cell's ability to produce energy and allow a buildup of lactic acid, a waste product. Many enzymes are involved in pyruvate metabolism. A hereditary deficiency in any one of these enzymes results in one of a variety of disorders, depending on which enzyme is missing. Symptoms may develop any time between early infancy and late adulthood. Exercise and infections can worsen symptoms, leading to severe lactic acidosis. These disorders are diagnosed by measuring enzyme activity in cells from the liver or skin.

Pyruvate dehydrogenase complex deficiency is a lack of a group of enzymes needed to process pyruvate. This deficiency results in a variety of symptoms, ranging from mild to severe. Some newborns with this deficiency have brain malformations. Other children appear normal at birth but develop symptoms, including weak muscles, seizures, poor coordination, and a severe balance problem, later in infancy or childhood. Mental retardation is common. This disorder cannot be cured, but some children are helped by a diet that is high in fat and low in carbohydrates.

Absence of pyruvate carboxylase, an enzyme, is a very rare condition that interferes with or blocks the production of glucose from pyruvate in the body. Lactic acid and ketones build up in the blood. Often this disease is fatal. Children who survive have seizures and severe mental retardation, although there are recent reports of children with milder symptoms. There is no cure, but some children are helped by eating frequent carbohydrate-rich meals and restricting dietary protein.