Clinical Information

Pyruvic acid, an intermediate metabolite, plays an important role in linking carbohydrate and amino acid metabolism to the tricarboxylic acid cycle, the fatty acid beta-oxidation pathway, and the mitochondrial respiratory chain complex. Though isolated elevated pyruvate is not diagnostic of any inborn error of metabolism, analysis with lactate may suggest an inborn error of metabolism as some present with lactic acidosis or a high lactate-to-pyruvate (L:P) ratio.

The L:P ratio is elevated in several, but not all, mitochondrial respiratory chain disorders. Mitochondrial disorders vary widely in presentation and age of onset. Many mitochondrial disorders have neurologic and myopathic features and may involve multiple organ systems. Determination of lactate, pyruvate, and L:P ratio in cerebrospinal fluid is helpful in directing attention toward a possible mitochondrial disorder in cases with predominantly neurologic dysfunction and normal blood lactate levels, though further confirmatory testing will be required to establish a diagnosis.

A low L:P ratio is observed in inherited disorders of pyruvate metabolism including pyruvate dehydrogenase complex (PDHC) deficiency. Clinical presentation of PDHC deficiency can range from fatal congenital lactic acidosis to relatively mild ataxia or neuropathy. The most common features in infants and children with PDHC deficiency are delayed development and hypotonia. Seizures and ataxia are also frequent features. Other manifestations can include congenital brain malformations, degenerative changes including Leigh disease, and facial dysmorphism.