Pyruvate metabolism disorders are carbohydrate metabolism disorders that are caused by a lack of the ability to metabolize a substance called pyruvate. These disorders cause a buildup of lactic acid and a variety of neurologic abnormalities. Pyruvate metabolism disorders occur when parents pass on to their children the defective genes that cause these disorders.
A deficiency in any one of the enzymes involved in pyruvate metabolism leads to one of many disorders.
Symptoms include seizures, intellectual disability, muscle weakness, and coordination problems.
Some specific pyruvate disorders are helped by changes in diet.
Some of these disorders can be fatal.
There are different types of inherited disorders. In many pyruvate metabolism disorders, both parents of the affected child carry 1 copy of the abnormal gene. Because usually 2 copies of the abnormal (recessive) gene are necessary for the disorder to occur, usually neither parent has the disorder. (See also Overview of Hereditary Metabolic Disorders.)
Pyruvate is a substance that is formed in the processing of carbohydrates and proteins and that serves as an energy source for cells.
Problems with the breaking down (metabolizing) of pyruvate can limit a cell’s ability to produce energy and allow a buildup of a waste product called lactic acid (lactic acidosis). 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 deficient.
Symptoms of pyruvate metabolism disorders 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 skin, by testing the person's DNA, or doing both.
Genetic testing, which is used to determine whether a couple is at increased risk of having a baby with a hereditary genetic disorder, is also available.
Pyruvate Dehydrogenase Deficiency
This disorder is caused by a lack of a group of enzymes needed to process pyruvate.
Pyruvate dehydrogenase 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. Intellectual disability is common.
This disorder cannot be cured, but some children are helped by a diet that is high in fat or low in carbohydrates. Children may also be given supplements of the vitamin thiamin.
Pyruvate Carboxylase Deficiency
Pyruvate carboxylase is an enzyme. A lack or deficiency of this enzyme causes 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 disorder is fatal. Children who survive may have developmental delay, seizures, failure to thrive, and intellectual disability. Some children have milder symptoms.
There is no effective treatment for this disorder, but, in some children, symptoms may be alleviated by managing the diet and by taking supplements of thiamin.
More Information
The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.
National Organization for Rare Disorders (NORD): This resource provides information to parents and families about rare diseases, including a list of rare diseases, support groups, and clinical trial resources.
Genetic and Rare Diseases Information Center (GARD): This resource provides and easy to understand information about rare or genetic diseases.
