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The treatment of congenital lactic acidoses

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Journal of Inherited Metabolic Disease

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.

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References

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Arnold DL, Taylor DJ, Radda GK (1985) Investigation of human mitochondrial myopathies by phosphorus magnetic resonance spectroscopy.Ann Neurol 18: 189–196.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Beal MF (1992) Does impairment of energy metabolism lead to excitotoxic neuronal death in neurodegenerative illnesses?Ann Neurol 31: 119–130.

    PubMed  Google Scholar 

  • 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 

  • Bernsen PL, Gabreels FJ, Ruitenbeek W, Hamburger HL (1993) Treatment of complex I deficiency with riboflavin.J Neurol Sci 118: 181–187.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Brown GK (1994) Metabolic disorders of embryogenesis.J Inher Metab Dis 17: 448–458.

    PubMed  Google Scholar 

  • Burlina AB, Milanesi O, Biban P, et al (1993) Beneficial effect of sodium dichloroacetate in muscle cytochromec oxidase deficiency.Eur J Pediatr 152: 537.

    PubMed  Google Scholar 

  • Chance B, Sies H, Boveris A (1979) Hydrogen peroxide metabolism in mammalian organs.Phys Rev 59: 527–605.

    Google Scholar 

  • Chrzanowska-Lightowlers ZMA, Lightowlers RN, Turnbull DM (1995) Gene therapy for mitochondrial disorders: is it possible?Gene Ther 2: 311–316.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • DiMauro S, Nicholson JF, Hays P (1983) Benign infantile mitochondrial myopathy due to a reversible cytochromec oxidase deficiency.Ann Neurol 14: 226–234.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Fujii T, Van Coster RN, Old SE, et al (1994) Pyruvate dehydrogenase deficiency: molecular basis for intrafamilial heterogeneity.Ann Neurol 36: 83–89.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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 

  • 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.

    PubMed  Google Scholar 

  • Narisawa K, Endo H, Miyabayashi S, Tada K (1992) Thiamine responsive pyruvate dehydrogenase deficiency.J Nutr Sci Vitaminol Tokyo 585–588.

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Radda GK, Bore PJ, Gadian DG, et al (1982)31P NMR examination of two patients with NADH-CoQ reductase deficiency.Nature 295: 608–609.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • Tulinius MH, Eriksson BO, Hjalmarson O, Holme E, Oldfors A (1989) Mitochondrial myopathy and cardiomyopathy in siblings.Pediatr Neurol 5: 182–188.

    PubMed  Google Scholar 

  • Van Erven PMM, Cillessen JPM, Eekhoof EMW, et al (1987) Leigh syndrome, a mitochondrial encephalo(myo)pathy.Clin Neurol Neurosurg 89: 217–230.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

  • 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.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Metabolic Unit, London Centre for Paediatric Endocrinology and Metabolism, Institute of Child Health, 30, Guilford Street, WC1N 1EH, London, UK

    A. A. M. Morris & J. V. Leonard

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  1. A. A. M. Morris
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  2. J. V. Leonard
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Morris, A.A.M., Leonard, J.V. The treatment of congenital lactic acidoses. J Inherit Metab Dis 19, 573–580 (1996). https://doi.org/10.1007/BF01799117

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  • DOI: https://doi.org/10.1007/BF01799117

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