European Journal of Pediatrics

, Volume 140, Issue 2, pp 98–101

Lacticacidosis, neurological deterioration and compromised cellular pyruvate oxidation due to a defect in the reoxidation of cytoplasmically generated NADH

  • B. H. Robinson
  • Jennifer Taylor
  • B. Francois
  • A. L. Beaudet
  • D. F. Peterson
Original Investigations


Two patients, one dying at 25 days and one at 20 months had ‘chronic’ lactic acidaemia with a high lactate to pyruvate ratio. Both showed EEG abnormalities and seizure activity and both died of respiratory failure. Investigation of cultured skin fibroblasts from these patients revealed normal pyruyate dehydrogenase and pyruvate carboxylase activities but the cells showed a decreased ability to oxidise pyruvate which was returned to normal on the addition of methylene blue. Subsequent investigations revealed that the mitochondria from the patients' cells could oxidise pyruvate normally but that the cells had an abnormal NAD to NADH ratio under standard conditions of incubation. It was concluded that both children had a redox disequilibrium in the cytoplasmic compartment due to a problem in transporting reducing equivalents from the cytoplasmic to the mitochondrial compartments.

Key words

Lacticacidosis Neurological deterioration Redox disequilibrium 


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  1. 1.
    Atkin BM, Utter MF, Weinberg MB (1979) Pyruvate carboxylase and phosphoenolpyruvate activity in leukocytes and fibroblasts from a patient with pyruvate carboxylase deficiency. Pediatr Res 13:38–43Google Scholar
  2. 2.
    Blass JP, Avigan J, Uhlendorf BW (1970) A defect in pyruvate decarboxylase in a child with an inte mittet movement disorder. J Clin Invest 49:423–432Google Scholar
  3. 3.
    Bucher T, Czok R, Lamprecht W, Latzko E (1965) Pyruvate. In: Bergemyer HU (ed) Methods in enzymatic analysis. Academic Press, New York, pp 253–259Google Scholar
  4. 4.
    Hohorst HJ (1965) L(+)-Lactate. In: Bergemyer HU (ed) Methods in enzymatic analysis. Academic Press, New York, pp 266–275Google Scholar
  5. 5.
    Howarth JC, Robinson BH, Perry TL (1981) Lactic acidosis due to pyruvate carboxylase deficiency. J Inherited Metab Dis 4: 57–58Google Scholar
  6. 6.
    Howell RR, Ashton DM, Wyngaarden JB (1962) Glucose-6-phosphatase deficiency glycogen storage disease. Studies on the interrelationships of carbohydrate, lipid, and purine abnormalitis. Pediatrics 29:553–565Google Scholar
  7. 7.
    Oliva PB (1970) Lactic acidosis. Am J Med 48 209Google Scholar
  8. 8.
    Pagliara AS, Karl TE, Keating JP, Brown BI, Kipnis DM (1972) Hepatic fructose 1,6-diphosphatase deficiency. J Clin Invest 51:2115–2119Google Scholar
  9. 9.
    Robinson BH, Halperin ML (1970) Transport of reduced nicotinamide adenine dinucleotide into mitochondria of white adipose tissue. Biochem J 116:229–234Google Scholar
  10. 10.
    Robinson BH, Sherwood WG (1970) Pyruvate dehydrogenase phosphatase deficiency: a cause of congenital lactic acidosis in infancy. Pediatr Res 9:935–939Google Scholar
  11. 11.
    Robinson BH, Taylor J, Sherwood WG (1977) Deficiency of dihydrolipoyl dehydrogenase (a component of the pyruvate and α-keto glutarate dehydrogenase complexes): a cause of congenital chronic lactic acidosis in infancy. Pediatr Res 11:1198–1202Google Scholar
  12. 12.
    Robinson BH, Taylor J, Sherwood WG (1980) The genetic heterogeneity of lactic acidosis. Occurrence of recognisable inborn errors of metabolism in a pediatric population with lactic acidosis. Pediatr Res 14:956–962Google Scholar
  13. 13.
    Slein MM (1965) Determination of glucose with hexokinase. In: Bergemyer HU (ed) Methods in enzymatic analysis. Academic Press, New York, p 117Google Scholar
  14. 14.
    Tranguada RE, Bernstein S, Grant WJ (1963) Methylene blue in the treatment of lactic acidosis. Clin Res 11:230–235Google Scholar
  15. 15.
    Willems JL, Monnens LAH, Trijbels JMF, Veerkamp JH, Meyer AEFH, Van Dam K, Van Haelst U (1977) Leigh's encephalomyelopathy in a patient with cytochrome c oxidase deficiency in muscle tissue. Pediatrics 60:850–857Google Scholar
  16. 16.
    Williamson JR, Corkey B (1969) Assays of intermediates of the citric acid cycle and related compounds by fluorimetric enzyme methods. Methods Enzymol 13:435–513Google Scholar
  17. 17.
    Williamson JR, Safer B, Lanoue KF, Smith CM, Watajtys E (1973) Mitochondrial cytosolic interactions in cardiac tissue. Role of the malate aspartate cycle in the removal of glycolytic NADH from the cytosol. Proc Soc Exp Biol Symposium 27, Cambridge University Press, p 241Google Scholar
  18. 18.
    Zebe S, Delbruck A, Bucher Th (1959) Über den glycerin-1-P cyclus im Flugmuskel von Lucusta migratioria. Biochem Z 331:254–272Google Scholar
  19. 19.
    Zeilke HR, Ozand PT, Tildon JT, Sevdalien DA, Cornblath M (1976) Growth of human diploid fibroblasts in the absence of glucose utilization. Proc Natl Acad Sci USA 72:4110–4114Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • B. H. Robinson
    • 1
    • 5
  • Jennifer Taylor
    • 1
    • 5
  • B. Francois
    • 3
  • A. L. Beaudet
    • 4
    • 2
  • D. F. Peterson
    • 4
    • 2
  1. 1.Departments of Paediatrics and BiochemistryUniversity of TorontoTorontoCanada
  2. 2.Department of Research InstituteThe Hospital for Sick ChildrenTorontoCanada
  3. 3.Centre de Neurologie PediatriqueUniversite Catholique de LouvainBrusselsBelgium
  4. 4.Department of PaediatricsBaylor College of MedicineHoustonUSA
  5. 5.Texas Children's HospitalHoustonUSA

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