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Pyruvate Metabolism Disorders

By

Matt Demczko

, MD, Sidney Kimmel Medical College of Thomas Jefferson University

Last full review/revision Apr 2020| Content last modified Apr 2020
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Pyruvate dehydrogenase deficiency

Clinical manifestations vary in severity but include lactic acidosis and central nervous system malformations and other postnatal changes, including cystic lesions of the cerebral cortex, brain stem, and basal ganglia; ataxia; and psychomotor retardation.

There is no clearly effective treatment for pyruvate dehydrogenase deficiency, although a low-carbohydrate or ketogenic diet and dietary thiamin supplementation have been beneficial for some patients.

Pyruvate carboxylase deficiency

Pyruvate carboxylase is an enzyme important for gluconeogenesis from pyruvate and alanine generated in muscle. Deficiency may be primary, or secondary to deficiency of holocarboxylase synthetase, biotin, or biotinidase; inheritance for both is autosomal recessive Autosomal Recessive Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more , and both result in lactic acidosis.

Primary deficiency incidence is < 1/250,000 births but may be higher in certain American Indian populations. Psychomotor retardation with seizures and spasticity are the major clinical manifestations. Laboratory abnormalities include hyperammonemia; lactic acidosis; ketoacidosis; elevated levels of plasma lysine, citrulline, alanine, and proline; and increased excretion of alpha-ketoglutarate.

Secondary deficiency is clinically similar, with failure to thrive, seizures, and other organic aciduria.

Diagnosis of pyruvate carboxylase deficiency is confirmed by enzyme analysis of cultured skin fibroblasts or DNA analysis.

There is no effective treatment for pyruvate carboxylase deficiency, but some patients with primary deficiency and all those with secondary deficiencies should be given biotin supplementation 5 to 20 mg orally once a day.

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