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Organic acids in urine of patients with congenital lactic acidoses: An aid to differential diagnosis

  • Disorders Of The Respiratory Chain And The Lactic Acidaemias
  • Published:
Journal of Inherited Metabolic Disease

Abstract

The differential diagnosis of patients with apparent congenital lactic acidoses poses one of the most intractable problems in the study of patients with disorders of organic acid metabolism. An outline of the factors leading to a lactic acidosis, particularly in infants and young children, together with a brief review of the known causes of congenital lactic acidosis, are presented. Quantitative examination of the organic acids excreted by patients with proven enzyme deficiencies causing congenital lactic acidosis has demonstrated the characteristic patterns that are associated with specific disorders of this kind. After exclusion of uninherited, acquired and secondary metabolic causes of lactic acidosis, these quantitative patterns of organic acid excretion, together with other clinical and biochemical observations, provide valuable indicators of the area of the underlying primary metabolic disorder for subsequent selected, confirmatory, enzymology. The study of organic acids has a key and central role in the approach to the clinical and biochemical investigation and diagnosis of patients with congenital lactic acidoses.

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References

  • Atkin, B. M., Buist, N. R. M., Utter, M. F., Leiter, A. B. and Banker, B. Q. Pyruvate carboxylase deficiency and lactic acidosis in a retarded child without Leigh’s disease.Pediatr. Res. 13 (1979) 109–116

    PubMed  CAS  Google Scholar 

  • Baal, M. G., Gabreëls, F. J. M., Renier, W. O., Hommes, F. A., Gijsbers, Th. H. J., Lamars, K. J. B. and Kok, J. C. N. A patient with pyruvate carboxylase deficiency in the liver: Treatment with aspartic acid and thiamine.Dev. Med. Child Neurol. 23 (1981) 521–530

    PubMed  CAS  Google Scholar 

  • Burman, D., Holton, J. B. and Pennock, C. A.Inherited Disorders of Carbohydrate Metabolism, MTP Press, Lancaster, 1980

    Google Scholar 

  • Cederbaum, S. D., Blass, J. P., Minkoff, N., Brown, W. J., Cotton, M. E. and Harris, S. H. Sensitivity to carbohydrate in a patient with familial intermittant lactic acidosis and pyruvate dehydrogenase deficiency.Pediatr. Res. 10 (1976) 713–720

    Article  PubMed  CAS  Google Scholar 

  • Chalmers, R. A. and Lawson, A. M.Organic Acids in Man. The Analytical Chemistry, Biochemistry and Diagnosis of the Organic Acidurias, Chapman & Hall, London, 1982

    Google Scholar 

  • Chalmers, R. A., Lawson, A. M. and Borud, O. Gas chromatographic and mass spectrometric studies on urinary organic acids in a patient with congenital lactic acidosis due to pyruvate decarboxylase deficiency.Clin. Chim. Acta 77 (1977) 117–124

    Article  PubMed  CAS  Google Scholar 

  • Chalmers, R. A., Ryman, B. E. and Watts, R. W. E. Studies on a patient within vivo evidence of type I glycogenosis and normal enzyme activitiesin vitro.Acta Paediatr. Scand. 67 (1978) 201–207

    Article  PubMed  CAS  Google Scholar 

  • Clark, J. B., Hayes, D. J., Byrne, E. and Morgan-Hughes, J. A. Mitochondrial myopathies: defects in mitochondrial metabolism in human skeletal muscle.Biochem. Soc. Trans. 11 (1983) 626–627

    PubMed  CAS  Google Scholar 

  • Clark, J. B., Hayes, D. J., Morgan-Hughes, J. A. and Byrne, E. Mitochondrial myopathies: disorders of the respiratory chain and oxidative phosphorylation.J. Inher. Metab. Dis. 7 Suppl. 1 (1984) 62–68

    Article  PubMed  CAS  Google Scholar 

  • Coudé, F. X., Ogier, H., Marsac, C., Munnich, A., Charpentier, C. and Saudubray, J. M. Secondary citrullinemia with hyperammonemia in four neonatal cases of pyruvate carboxylase deficiency.Pediatrics 68 (1981) 914 (C)

    PubMed  Google Scholar 

  • De Vivo, D. C., Haymond, M. W., Leckie, M. P., Bursmann, Y. L., McDougal, D. B. and Pagliara, A. S. The clinical and biochemical implications of pyruvate carboxylase deficiency.J. Clin. Exp. Med. 45 (1977) 1281–1296

    Google Scholar 

  • Farrell, D. F., Clark, A. F., Scott, R. C. and Wennberg, R. P. Absence of pyruvate decarboxylase activity in man: A cause of congenital lactic acidosis.Science 187 (1975) 1082–1084

    Article  PubMed  CAS  Google Scholar 

  • Fiser, R. H., Melsher, H. L. and Fisher, D. A. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) deficiency. A new cause of hypoglycemia in childhood.Pediatr. Res. 8 (1974) 432 (Abstr.)

    Google Scholar 

  • Hommes, F. A., Bendien, K., Elema, J. D., Bremer, H. J. and Lombeck, I. Two cases of phosphoenolpyruvate carboxykinase deficiency.Acta Paediatr. Scand. 65 (1976) 233–240

    Article  PubMed  CAS  Google Scholar 

  • Kodama, H., Okada, S., Inui, K., Yutaka, T. and Yabuchi, H. Studies on α-ketoglutaric aciduria in type I glycogenosis.Tohoku J. Exp. Med. 131 (1980) 347–353

    Article  PubMed  CAS  Google Scholar 

  • Kuhara, T., Shinka, T., Inoue, Y., Matsumoto, M., Yoshvio, M., Sakaguchi, Y. and Matsumoto, I. Studies of urinary organic acid profiles of a patient with dihydrolipoyl dehydrogenase deficiency.Clin. Chim. Acta 133 (1983) 133–140

    Article  PubMed  CAS  Google Scholar 

  • Kuroda, Y., Kline, J. J., Sweetman, L., Nyhan, W. L. and Groshong, T. D. Abnormal pyruvate and α-ketoglutarate dehydrogenase complexes in a patient with lactic acidemia.Pediatr. Res. 13 (1979) 928–931

    Article  PubMed  CAS  Google Scholar 

  • Morgan-Hughes, J. A., Darveniza, P., Kahn, S. N., Landon, D. N., Sherratt, R. M., Land, J. M. and Clark, J. B. A mitochondrial myopathy characterised by a deficiency in reducible cytochrome b.Brain 100 (1977) 617–640

    Article  PubMed  CAS  Google Scholar 

  • Munnich, A., Saudubray, J. M., Taylor, J., Charpentier, C., Marsac, C., Rocchiccioli, F., Amédée-Manesme, O., Coudé, F. X. Frézal, J. and Robinson, B. H. Congenital lactic acidosis, α-ketoglutaric aciduria and variant form of maple syrup urine disease due to a single enzyme defect: Dihydrolipoyl dehydrogenase deficiency.Acta Paediatr. Scand. 71 (1982) 167–171

    Article  PubMed  CAS  Google Scholar 

  • Robinson, B. H. Inborn errors of pyruvate metabolism.Biochem. Soc. Trans. 11 (1983) 623–626

    PubMed  CAS  Google Scholar 

  • Robinson, B. H. and Sherwood, W. G. Pyruvate dehydrogenase phosphatase deficiency: A cause of congenital chronic lactic acidosis in infancy.Pediatr. Res. 9 (1975) 935–939

    Article  PubMed  CAS  Google Scholar 

  • Robinson, B. H. and Sherwood, W. G. Lactic acidaemia.J. Inker. Metab. Dis. 7 Suppl. 1 (1984) 69–73

    Article  CAS  Google Scholar 

  • Robinson, B. H., Taylor, J., Kahler, S. G. and Kirkman, H. N. Lactic acidemia, neurologic deterioration and carbohydrate dependence in a girl with dihydrolipoyl dehydrogenase deficiency.Eur. J. Paediatr. 136 (1981) 35–39

    Article  CAS  Google Scholar 

  • Robinson, B. H., Taylor, J. and Sherwood, W. G. Deficiency of dihydrolipoyl dehydrogenase (a component of the pyruvate and α-ketoglutarate dehydrogenase complexes): a cause of congenital chronic lactic acidosis in infancy.Pediatr. Res. 11 (1977) 1198–1202

    PubMed  CAS  Google Scholar 

  • Robinson, B. H., Taylor, J. and Sherwood, W. G. The genetic heterogeneity of lactic acidosis: Occurrence of recognisable inborn errors of metabolism in a paediatric population with lactic acidosis.Pediatr. Res. 14 (1980) 956–982

    PubMed  CAS  Google Scholar 

  • Saudubray, J. M., Marsac, C., Charpentier, C., Cathelineau, L., Besson Leaud, M. and Leroux, J. P. Neonatal congenital lactic acidosis with pyruvate carboxylase deficiency in two siblings.Acta Paediatr. Scand. 65 (1976) 717–724

    PubMed  CAS  Google Scholar 

  • Strömme, J. H., Borud, O. and Moe, P. J. Fatal lactic acidosis in a newborn attributable to a congenital defect of pyruvate dehydrogenase.Pediatr. Res. 10 (1976) 62–66

    PubMed  Google Scholar 

  • Taylor, J., Robinson, B. H. and Sherwood, W. G. A defect in branched-chain amino acid metabolism in a patient with congenital lactic acidosis due to dihydrolipoyl dehydrogenase deficiency.Pediatr. Res. 12 (1978) 60–62

    Article  PubMed  CAS  Google Scholar 

  • Tracey, B. M., Stacey, T. E. and Chalmers, R. A. Urinary and plasma organic acids in dizygotic twin siblings with 3-hydroxy-3-methylglutaric aciduria, studied by gas chromatography and mass spectrometry using fused silica capillary columns.J. Inker. Metab. Dis. 6 Suppl 2 (1983) 125–126

    Article  Google Scholar 

  • Van Biervliet, J. P. G. M., Bruinvis, L., Ketting, D., de Bree, P. K., Van der Heiden, C., Wadman, S. K., Willems, J. L., Bookelman, H., Van Haelst, V. and Monnens, L. A. H. Hereditary mitochondrial myopathy with lactic acidaemia, a deToni-Fanconi-Debré Syndrome, and a defective respiratory chain in voluntary striated muscles.Pediatr. Res. 11 (1977a) 1088–1093

    Article  PubMed  Google Scholar 

  • Van Biervliet, J. P. G. M., Bruinvis, L., Van der Heiden, C., Ketting, D., Wadman, S. K., Willems, J. L. and Monnens, L. A. H. Report of a patient with severe, chronic lactic acidaemia and pyruvate carboxylase deficiency.Dev. Med. Child Neurol. 19 (1977b) 392–401

    Article  PubMed  Google Scholar 

  • Vidnes, J. and Søvik, O. Gluconeogenesis in infancy and childhood. III. Deficiency of extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase in a case of persistent neonatal hypoglycaemia.Acta Paediatr. Scand. 65 (1976) 307–312

    Article  PubMed  CAS  Google Scholar 

  • Willems, J. L. Disturbances in pyruvate metabolism. A biochemical and clinical investigation. Thesis, Catholic University of Nijmegen, 1978

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  1. Paediatric Research Group, MRC Clinical Research Centre, Watford Road, HA1 3 UJ, Harrow, UK

    R. A. Chalmers

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Chalmers, R.A. Organic acids in urine of patients with congenital lactic acidoses: An aid to differential diagnosis. J. Inher. Metab. Dis. 7 (Suppl 1), 79–89 (1984). https://doi.org/10.1007/BF03047380

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