Journal of Inherited Metabolic Disease

, Volume 19, Issue 4, pp 573–580 | Cite as

The treatment of congenital lactic acidoses

  • A. A. M. Morris
  • J. V. Leonard
Article

Summary

Congenital lactic acidoses form a heterogeneous group of disorders: this paper considers primarily defects of the pyruvate dehydrogenase complex and the respiratory chain. Attempts to treat these disorders are hampered by uncertainty concerning the pathophysiology and by the central role of the enzymes in cellular metabolism. Few strategies are of proven efficacy, though many have been tried, including dietary manipulation, enhancement of residual enzyme activity, artificial electron acceptors and free-radical scavengers. Evaluation of treatment is complicated by the rarity, heterogeneity and unpredictable course of the diseases. Double-blind placebo-controlled trials are needed.

Keywords

Public Health Enzyme Activity Internal Medicine Pyruvate Metabolic Disease 

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References

  1. Abe K, Fujimura H, Nishikawa Y, et al (1991) Marked reduction in CSF lactate and pyruvate levels after CoQ therapy in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).Acta Neurol Scand 83: 356–359.PubMedGoogle Scholar
  2. Arnold DL, Matthews PM, Radda GK (1984) Metabolic recovery after exercise and the assessment of mitochondrial functionin vivo in human skeletal muscle by means of31P NMR.Magn Reson Med 1: 307–315.PubMedGoogle Scholar
  3. Arnold DL, Taylor DJ, Radda GK (1985) Investigation of human mitochondrial myopathies by phosphorus magnetic resonance spectroscopy.Ann Neurol 18: 189–196.PubMedGoogle Scholar
  4. Arts WF, Scholte HR, Bogaard JM, Kerrebijn KG, Luyt-Houwen IE (1983) NADH-CoQ reductase deficient myopathy: successful treatment with riboflavin.Lancet 2: 581–582.PubMedGoogle Scholar
  5. Bakker HD, Scholte HR, Jeneson JA, Busch HF, Abeling NG, van Gennip AH (1994) Vitamin-responsive complex I deficiency in a myopathic patient with increased activity of the terminal respiratory chain and lactic acidosis.J Inher Metab Dis 17: 196–204.PubMedGoogle Scholar
  6. Beal MF (1992) Does impairment of energy metabolism lead to excitotoxic neuronal death in neurodegenerative illnesses?Ann Neurol 31: 119–130.PubMedGoogle Scholar
  7. Bendahan D, Desnuelle C, Vanuxem D, et al (1992)31P NMR spectroscopy and ergometer exercise test as evidence for muscle oxidative performance improvement with coenzyme Q in mitochondrial myopathies.Neurology 42: 1203–1208.Google Scholar
  8. Bernsen PL, Gabreels FJ, Ruitenbeek W, Hamburger HL (1993) Treatment of complex I deficiency with riboflavin.J Neurol Sci 118: 181–187.PubMedGoogle Scholar
  9. Bonne G, Benelli C, De-Meirleir L, et al (1993) El pyruvate dehydrogenase deficiency in a child with motor neuropathy.Pediatr Res 33: 284–288.PubMedGoogle Scholar
  10. Bourgeron T, Rustin P, Chretien D, et al (1995) Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency.Nature Genetics 11: 144–149.PubMedGoogle Scholar
  11. Bresolin N, Doriguzzi C, Ponzetto C, et al (1990) Ubidecarenone in the treatment of mitochondrial myopathies: a multi-center double-blind trial.J Neurol Sci 100: 70–78.PubMedGoogle Scholar
  12. Brown GK (1994) Metabolic disorders of embryogenesis.J Inher Metab Dis 17: 448–458.PubMedGoogle Scholar
  13. Burlina AB, Milanesi O, Biban P, et al (1993) Beneficial effect of sodium dichloroacetate in muscle cytochromec oxidase deficiency.Eur J Pediatr 152: 537.PubMedGoogle Scholar
  14. Chance B, Sies H, Boveris A (1979) Hydrogen peroxide metabolism in mammalian organs.Phys Rev 59: 527–605.Google Scholar
  15. Chrzanowska-Lightowlers ZMA, Lightowlers RN, Turnbull DM (1995) Gene therapy for mitochondrial disorders: is it possible?Gene Ther 2: 311–316.PubMedGoogle Scholar
  16. De Stefano N, Matthews PM, Ford B, Genge A, Karpati G, Arnold DL (1995) Short-term dichloroacetate treatment improves indices of cerebral metabolism in patients with mitochondrial disorders.Neurology 45: 1193–1198.PubMedGoogle Scholar
  17. DiMauro S, Nicholson JF, Hays P (1983) Benign infantile mitochondrial myopathy due to a reversible cytochromec oxidase deficiency.Ann Neurol 14: 226–234.PubMedGoogle Scholar
  18. Eleff S, Kennaway NG, Buist NRM, et al (1984)31P NMR study of improvement in oxidative phosphorylation by vitamins K3 and C in a patient with a defect in electron transport at complex III in skeletal muscle.Proc Natl Acad Sci USA 81: 3529–3533.PubMedGoogle Scholar
  19. Falk RE, Cederbaum SD, Blass JP, Gibson GE, Pieter Kark RA, Carrel RE (1976) Ketogenic diet in the management of pyruvate dehydrogenase deficiency.Pediatrics 58: 713–721.PubMedGoogle Scholar
  20. Fujii T, Van Coster RN, Old SE, et al (1994) Pyruvate dehydrogenase deficiency: molecular basis for intrafamilial heterogeneity.Ann Neurol 36: 83–89.PubMedGoogle Scholar
  21. Griebel V, Krageloh-Mann I, Ruitenbeek W, Trijbels JM, Paulus W (1990) A mitochondrial myopathy in an infant with lactic acidosis.Dev Med Child Neurol 32: 528–531.PubMedGoogle Scholar
  22. Ihara Y, Namba R, Kuroda S, Sato T, Shirabe T (1989) Mitochondrial encephalomyopathy (MELAS): pathological study and successful therapy with coenzyme Q10 and idebenone.J Neurol Sci 90: 263–271.PubMedGoogle Scholar
  23. Krageloh-Mann I, Grodd W, Niemann G, Haas G, Ruitenbeek W (1992) Assessment and therapy monitoring of Leigh disease by MRI and proton spectroscopy.Pediatr Neurol 8: 60–64.PubMedGoogle Scholar
  24. Matalon R, Stumpf DA, Michals K, Hart RD, Parks JK, Goodman SI (1984) Lipoamide dehydrogenase deficiency with primary lactic acidosis: favourable response to treatment with oral lipoic acid.J Pediatr 104: 65–69.PubMedGoogle Scholar
  25. Matthews PM, Ford B, Dandurand RJ, et al (1993) Coenzyme Q10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease.Neurology 43: 884–890.PubMedGoogle Scholar
  26. Morris A, Bindoff LA, Jackson MJ, et al (1995) Neonatal Fanconi syndrome and lactic acidosis due to deficiency of complex III of the mitochondrial respiratory chain.Pediatr Nephrol 9: 547–551.Google Scholar
  27. Naito E, Ito M, Takeda E, Yokota I, Yoshijima S, Kuroda Y (1994) Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine-responsive congenital lactic acidemia.Pediatr Res 36: 340–346.PubMedGoogle Scholar
  28. Narisawa K, Endo H, Miyabayashi S, Tada K (1992) Thiamine responsive pyruvate dehydrogenase deficiency.J Nutr Sci Vitaminol Tokyo 585–588.Google Scholar
  29. Nishikawa Y, Takahashi M, Yorifuji S, et al (1989) Long-term coenzyme Q10 therapy for a mitochondrial encephalomyopathy with cytochromec oxidase deficiency: a31P NMR study.Neurology 39: 399–493.PubMedGoogle Scholar
  30. Ogasahara S, Engel AG, Frens D, Mack D (1989) Muscle coenzyme Q deficiency in familial mitochondrial encephalomyopathy.Proc Natl Acad Sci USA 86: 2379–2382.PubMedGoogle Scholar
  31. Ostman-Smith I, Brown G, Johnson A, Land J (1994) Dilated cardiomyopathy due to type II X-linked 3-methylglutaconic aciduria: successful treatment with pantothenic acid.Br Heart J 72: 349–353.PubMedGoogle Scholar
  32. Penn AM, Lee JW, Thuillier P, et al (1992) MELAS syndrome with mitochondrial tRNA(Leu)(UUR) mutation: correlation of clinical state, nerve conduction, and muscle31P magnetic resonance spectroscopy during treatment with nicotinamide and riboflavin.Neurology 42: 2147–2152.PubMedGoogle Scholar
  33. Piccolo G, Banfi P, Azan G, et al (1991) Biological markers of oxidative stress in mitochondrial myopathies with progressive external ophthalmoplegia.J Neurol Sci 105: 57–60.PubMedGoogle Scholar
  34. Radda GK, Bore PJ, Gadian DG, et al (1982)31P NMR examination of two patients with NADH-CoQ reductase deficiency.Nature 295: 608–609.PubMedGoogle Scholar
  35. Robinson BH, MacMillan H, Petrova-Benedict R, Sherwood WG (1987) Variable clinical presentation in patients with deficiency of the pyruvate dehydrogenase complex. A review of 30 cases with deficiency of the E1 component of the complex.J Pediatr 111: 525–533.PubMedGoogle Scholar
  36. Roodhooft AM, Van Acker KJ, Martin JJ, Ceuterick C, Scholte HR, Luyt-Houwen IE (1986) Benign mitochondrial myopathy with deficiency of NADH-CoQ reductase and cytochromec oxidase.Neuropediatrics 17: 221–226.PubMedGoogle Scholar
  37. Saijo T, Naito E, Ito M, Takeda E, Hashimoto T, Kuroda Y (1991) Therapeutic effect of sodium dichloroacetate on visual and auditory hallucinations in a patient with MELAS.Neuropediatrics 22: 166–167.PubMedGoogle Scholar
  38. Scholte HR, Busch HF, Luyt-Houwen IE (1992) Vitamin-responsive pyruvate dehydrogenase deficiency in a young girl with external ophthalmoplegia, myopathy and lactic acidosis.J Inher Metab Dis 15: 331–334.PubMedGoogle Scholar
  39. Stacpoole PW, Wright EC, Baumgartner, et al (1992) A controlled clinical trial of dichloroacetate for treatment of lactic acidosis in adults. The Dichloroacetate-Lactic Acidosis Study Group.N Engl J Med 327: 1564–1569.PubMedGoogle Scholar
  40. Toth PP, el-Shanti H, Eivins S, Rhead WJ, Klein JM (1993) Transient improvement of congenital lactic acidosis in a male infant with pyruvate decarboxylase deficiency treated with dichloroacetate.J Pediatr 123: 427–430.PubMedGoogle Scholar
  41. Tulinius MH, Eriksson BO, Hjalmarson O, Holme E, Oldfors A (1989) Mitochondrial myopathy and cardiomyopathy in siblings.Pediatr Neurol 5: 182–188.PubMedGoogle Scholar
  42. Van Erven PMM, Cillessen JPM, Eekhoof EMW, et al (1987) Leigh syndrome, a mitochondrial encephalo(myo)pathy.Clin Neurol Neurosurg 89: 217–230.PubMedGoogle Scholar
  43. Wijburg FA, Barth PG, Bindoff LA, et al (1992) Leigh syndrome associated with a deficiency of the pyruvate dehydrogenase complex: results of treatment with a ketogenic diet.Neuropediatrics 23: 147–152.PubMedGoogle Scholar
  44. Zierz S, Jahns G, Jerusalem F (1989) Coenzyme Q in serum and muscle of 5 patients with Kearns-Sayre syndrome and 12 patients with ophthalmoplegia plus.J Neurol 236: 97–101.PubMedGoogle Scholar

Copyright information

© SSIEM and Kluwer Academic Publishers 1996

Authors and Affiliations

  • A. A. M. Morris
    • 1
  • J. V. Leonard
    • 1
  1. 1.Metabolic Unit, London Centre for Paediatric Endocrinology and MetabolismInstitute of Child HealthLondonUK

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