Metabolic intermediates in lactic acidosis: compounds, samples and interpretation
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A number of acquired conditions including infections, severe catabolic states, tissue anoxia, severe dehydration and poisoning can give rise to hyperlactacidaemia. All these causes should be ruled out before considering inborn errors of metabolism. Carefully collected samples are necessary if artefacts that results in spuriously increased lactate/pyruvate (L/P) and 3-hydroxybutyrate/acetoacetate (B/A) ratios are to be avoided. When properly performed, 24-h studies of L/P and B/A ratios provide a useful tool in making a diagnosis. A few metabolic profiles when present are specific or highly suggestive of a given disorder. When the L/P ratio is normal or low, pyruvate dehydrogenase (PDH) deficiency is highly probable whatever the lactate concentration, which is often only moderately elevated after meal, may be. When the L/P ratio is very high in association with post-prandial hyperketonaemia and in contrast to a normal or low B/A ratio, pyruvate carboxylase (PC) deficiency andα-ketoglutarate dehydrogenase (KGDH) deficiency are the most likely diagnoses. The distinction between the two disorders relies upon amino acid and organic acid profiles (glutamate andα-ketoglutarate accumulations in KGDH deficiency and hyperammonaemia and hypercitrullinaemia in PC deficiency). When both L/P and B/A ratios are elevated and associated with significant post-prandial hyperketonaemia, respiratory-chain disorders should first be suspected. All other profiles, especially a high L/P ratio without hyperketonaemia, are compatible with respiratory-chain disorders but are not specific; all acquired anoxic conditions should also be ruled out. Clearly, the clinical utility of these profiles needs to be interpreted cautiously in very ill patients in relation to the cardiocirculatory condition and to therapy. Finally, a normal profile, even after stress and loading, does not rule out an inborn error of lactate/pyruvate oxidation.
KeywordsGlutamate Metabolic Profile Lactate Concentration Anoxic Condition Lactic Acidosis
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- Aynsley-Green A, Williamson DH, Gitzelmann R (1977) The dietary treatment of glycogen synthetase deficiency.Helv Paediatr Acta 1: 71–75.Google Scholar
- Baumgartner R, Suormala T (1995) Biotin-responsive multiple carboxylase deficiency. In Fernandes J, Saudubray JM, Van den Berghe G, eds.Inborn Metabolic Diseases: Diagnosis and Treatment, 2nd edn. Berlin: Springer-Verlag, 239–245.Google Scholar
- Blass JP, Cederbaum SD, Gibson GE (1983) Clinical and metabolic abnormalities accompanying deficiencies in pyruvate oxidation. In Hommes FA, ed.Normal and Pathological Development of Energy Metabolism. New York: Wiley-Liss, 210–220.Google Scholar
- Coudé FX, Saudubray JM, Demaugre F, Marsac C, Leroux JP, Charpentier C (1978) Effect of dichloroacetate in congenital lactic acidosis.N Engl J Med 299: 1365–1366.Google Scholar
- Fernandes J, Chen Y (1995) Glycogen storage diseases. In Fernandes J, Saudubray JM, Van den Berghe G, eds.Inborn Metabolic Diseases: Diagnosis and Treatment, 2nd edn. Berlin: Springer-Verlag, 71–85.Google Scholar
- Fernandes J, Saudubray JM (1995) Diagnostic procedures: function tests and postmortem protocol. In Fernandes J, Saudubray JM, Van den Berghe G, eds.Inborn Metabolic Diseases: Diagnosis and Treatment, 2nd edn. Berlin: Springer-Verlag, 41–46.Google Scholar
- Kerr DS, Zinn AB (1995) The pyruvate dehydrogenase complex and tricarboxylic acid cycle. In Fernandes J, Saudubray JM, Van den Berghe G, eds.Inborn Metabolic Diseases: Diagnosis and Treatment, 2nd edn. Berlin: Springer-Verlag, 109–119.Google Scholar
- Medina JM, Tabernero A, Tovar JA, Martín-Barrientos J (1996) Metabolic fuel utilization and pyruvate oxidation during the postnatal period.J Inher Metab 19: 432–442.Google Scholar
- Robinson BH, Taylor J, Sherwood WG (1978) Deficiency of dihydrolipoyl dehydrogenase. A cause of congenital lactic acidosis in infancy.Pediatr Res 11: 1198–1203.Google Scholar
- Robinson BH, Oei J, Saudubray JM, et al (1987) The French and North American phenotypes of pyruvate carboxylase deficiency. Correlation with biotin containing protein by3H-biotin incorporation,35S-streptavidin labeling, and Northern blotting with a cloned cDNA probe.Am J Hum Genet 40: 50–59.PubMedGoogle Scholar
- Vassault A, Bonnefont JP, Specola N, Saudubray JM (1990) Lactate, pyruvate and ketone bodies. In Hommes FA, ed.Techniques in Diagnostic Human Biochemical Genetics. New York: Wiley-Liss, 285–308.Google Scholar