Clinical Information

Lactic acid (lactate) is primarily produced from glucose metabolism via the glycolytic pathway. Although primarily metabolized by the liver, other tissues also use small amounts of lactate. Typically, the amount of lactate produced parallels the amount utilized. Both the rates of lactate production and liver clearance impact the lactate concentration in blood. Lactic acidosis, or the accumulation of excess lactate, results from a combination of increased lactate production with decreased utilization.

Patients experiencing lactic acidosis present with tachypnea, weakness, and fatigue. Untreated, patients may develop confusion and progress to coma. Lactic acidosis may be associated with hypoxic conditions (eg, shock, hypovolemia, heart failure, pulmonary insufficiency), metabolic disorders (eg, diabetic ketoacidosis, malignancies, inborn errors of metabolism), and toxin exposures (eg, ethanol, methanol, salicylates).

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. However, pyruvic acid levels alone have little clinical utility.

Combined analysis of lactate and pyruvate may suggest an inborn error of metabolism when elevations of both analytes are observed or when there is an abnormal lactate-to-pyruvate (L:P) ratio. For example, several mitochondrial respiratory chain disorders exhibit elevated L:P ratios. Mitochondrial disorders vary widely in both clinical presentation and age of onset. Patients commonly present with neurologic and myopathic features. In addition, patients may experience involvement of multiple organ systems with features such as myopathy, ophthalmoplegia, ptosis, cardiomyopathy, sensorineural hearing loss, optic atrophy, pigmentary retinopathy, diabetes mellitus, encephalomyopathy, seizures, and stroke-like episodes.

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 observed in infants and children with PDHC deficiency are developmental delay, hypotonia, seizures, and ataxia. Other manifestations may include congenital brain malformations, degenerative changes including Leigh disease, and facial dysmorphism.