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Investigating possible disorders of mitochondrial metabolism, when used in conjunction with cerebrospinal fluid lactate collected at the same time to determine the lactate-to-pyruvate ratio
Evaluating patients with neurologic dysfunction and normal blood lactate-to-pyruvate ratios
The CSF lactate:pyruvate (L:P) ratio is considered a helpful (not diagnostic) tool in the evaluation of patients with possible disorders of mitochondrial metabolism, especially in patients with neurologic dysfunction and normal blood L:P ratios. Pyruvic acid levels alone have little clinical utility.
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 pyruvate is not diagnostic in itself, analysis with lactate has diagnostic value as many inborn errors of metabolism present with laboratory findings that include lactic acidosis and/or a high lactate: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 the 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.
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.
An elevated lactate-to-pyruvate (L:P) ratio may indicate inherited disorders of the respiratory chain complex, tricarboxylic acid cycle disorders and pyruvate carboxylase deficiency. Respiratory chain defects usually result in L:P ratios >20.
A low L:P ratio (disproportionately elevated pyruvic acid) may indicate an inherited disorder of pyruvate metabolism. Defects of the pyruvate dehydrogenase complex result in L:P ratios <10.
The L:P ratio is characteristically normal in other patients. An artifactually high ratio can be found in acutely ill patients.
Correct specimen collection and handling is crucial to achieve reliable results.
Pyruvic acid levels alone have little clinical utility. Abnormal concentrations of pyruvic acid, and lactate-to-pyruvate (L:P) ratios, are not diagnostic for a particular disorder but must be interpreted in the context of the patient's clinical presentation and other laboratory studies.
For the L:P ratio, both analytes should be determined on the same specimen.
When comparing blood and cerebrospinal fluid (CSF) L:P ratios, blood and CSF specimens should be collected at the same time.
1. Munnich A, Rotig A, Cormier-Daire V, Rustin P: Clinical Presentation of Respiratory Chain Deficiency. OMMBID. Accessed 10 Nov 2015. Available from URL: http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62677811
2. Robinson BH: Lactic acidemia: disorders of pyruvate carboxylase and pyruvate dehydrogenase. OMMBID. Accessed 10 Nov 2015. Available from URL: http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62633368
3. Shoffner JM: Oxidative Phosphorylation Diseases. OMMBID. Accessed 10 Nov 2015. Available from URL: http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62634554