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Therapy of complex I deficiency: Peripheral neuropathy during dichloroacetate therapy

  • Neuropediatrics
  • Original Paper
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Abstract

A therapeutic trial with polyvitamins and dichloroacetate (DCA) in combination with thiamine in a 13-year-old girl with complex I deficiency is reported. The polyvitamin therapy included thiamine, riboflavin, ascorbate, coenzyme Q 10 and carnitine. This therapeutic regine was used over a period of 17 months without any effect. Although DCA lowered the lactate concentration in blood and CNS — measured by magnetic resonance spectroscopy — no clinical benefit was achieved. After 20 weeks of DCA therapy a distal polyneuropathy with areflexia developed although 100 mg thiamine daily as comedication was given from the beginning of DCA therapy. Nerve conduction velocity of the peroneal nerve was not detectable, sensible evoked potentials of the tibialis posterious nerve were normal. This side-effect resolved completely within 6 months after omission of DCA. Our observation suggests a direct toxic effect of DCA only on the peripheral nervous system in our patient since several cerebral MRI and magnetic resonance spectroscopy studies showed no abnormalities.

Conclusion

DCA lowers the lactate concentration in children with complex I deficiency of the respiratory chain in a dose of 100 mg/kg body weight without clinical benefit. Reversible peripheral polyneuropathy may develop under DCA therapy despite thiamine medication.

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Abbreviations

DCA :

dichloroacetate

MRS :

magnetic resonance spectroscopy

MELAS :

mitochondrial encephalopathy, lactate acidosis, stroke like episodes

MERRF :

mitochondrial encephalopathy with ragged red fibres

References

  1. Arts WFM, Scholte HR, Bogaard JM, Kerrebijn KF, Luyt-Houwen JEM (1983) NADH-CoQ reductase deficient myopathy: successful treatment with riboflavin. Lancet II: 581–582

    Article  Google Scholar 

  2. Bernsen PLJ, Gabreels FJM, Ruitenbeck W, Sengers RCA, Stadhouders AM, Renier WO (1991) Successful treatment of pure myopathy, associated with complex I deficiency, with riboflavin and carnitin. Arch Neurol 48: 334–338

    PubMed  Google Scholar 

  3. Bottomley PA (1987) Spatial localisation in NMR spectroscopy in vivo. Ann NY Acad Sci 508: 333–348

    PubMed  Google Scholar 

  4. Clark JB, Hayes DJ, Morgan-Highes JA, Byrne E (1984) Mitochondrial myopathies: disorders of the respiratory chain and oxidative phosphorylation. J Inherited Metab Dis 7 [Suppl 1]: 62–68

    Article  Google Scholar 

  5. Evans OB (1985) Lactic acidosis in childhood: part I. Pediatr Neurol 1: 325–328

    Article  PubMed  Google Scholar 

  6. Fischer JC (1985) Mitochondrial myopathies and respiratory chain defects. Dissertation, University of Nijmegen

  7. Hammans SR, Morgan-Hughes JA (1994) Mitochondrial myopathies: clinical features, investigation, treatment and genetic counselling. In: Schapira AHV, DiMauro S (ed) Mitochondrial disorders in neurology. Butterworth-Heinemann, Oxford, pp 49–74

    Google Scholar 

  8. Ichiki T, Tanaka M, Nishikimi M, Suzuki H, Takayuki O, Kobayashi M, Wada Y (1988) Deficiency of subunits of complex I and mitochondrial encephalomyopathy. Ann Neurol 23: 287–294

    Article  PubMed  Google Scholar 

  9. Kudoroda Y, Ito M, Takeda E, Naito E, Hwang TJ, Hashimoto T, Miyado M, Masuda M, Yamashita K, Adachi T, Suzuki Y, Nishiyama K (1986) Treatment of chronic congenital lactic acidosis by oral administration of dichloracetate. J Inherited Metab Dis 9: 244–252

    Article  PubMed  Google Scholar 

  10. Kuroda Y, Natio E, Takeda E, Yokato I, Miyao M (1987) Congenital lactic acidosis. Enzyme 38: 108–114

    PubMed  Google Scholar 

  11. Koga Y, Nonaka I, Kobayashi M, Tojyo M, Nihei K (1988) Findings in muscle in complex I (NADH coenzyme Q reductase) deficiency. Ann Neurol 24: 749–756

    Article  PubMed  Google Scholar 

  12. Lilienthal JL, Zierler KL, Folk BP (1950) A reference base and system for analysis of muscle constituents. J Biol Chem 182: 501–508

    Google Scholar 

  13. McKhann C, Francois B, Evrard P (1980) Longterm use of lower doses of dichloracetate in a child with congenital lactic acidoses. Pediatr Res 14: 167

    Google Scholar 

  14. Moore GW, Swift LL, Rabinowitz D, Croford OB, Oates JA, Stacpole PW (1979) Reduction of serum cholesterol in two patients with homozygous familial hypercholesterolemia by dichloroacetate. Atherosclerosis 33: 285–293

    PubMed  Google Scholar 

  15. Morgan-Hughes JA, Hayes DJ, Cooper M, Clark JB (1985) Mitochondrial myopathies: deficiences localized to complex I and complex III of the mitochondrial respiratory chain. Bio Soc Trans 13: 648–650

    Google Scholar 

  16. Petty RKH, Harding AE, Morgan-Hughes JA (1986) The clinical features of mitochondrial myopathy. Brain 109: 915–938

    PubMed  Google Scholar 

  17. Przyrembel H (1987) Therapy of mitochondrial disorders. J Inherited Metab Dis 10: 129–146

    Article  PubMed  Google Scholar 

  18. Roodhooft AM, Acker KJ, Martin JJ, Ceuterick C, Scholte HR, Luyt-Houwen IEM (1986) Benign mitochondrial myopathy with deficiency of NADH-CoQ reductase and cytochrome c oxidase. Neuropediatrics 17: 221–226

    PubMed  Google Scholar 

  19. Schon EA (1994) Mitochondrial DNA and the genetics of mitochondrial disease. In: Schapira AHV, DiMauro S (ed) Mitochondrial disorders in neurology, Butterworth-Heinemann, Oxford, pp 31–48

    Google Scholar 

  20. Sottocasa GL, Kuylenstierna B, Ernester L (1967) An electrontransport system associated with the outer membrane of liver mitochondria. J Cell Biol 32: 415–438

    Article  PubMed  Google Scholar 

  21. Stacpole PW (1989) The pharmacology of dichloracetate. Metabolism 38: 1124–1144

    Article  PubMed  Google Scholar 

  22. Stitt M (1985) Citrate synthase. In: Bergmeyer HU (ed) Methods of enzymatic analysis, 3 rd edn. Vol IV, VCH-Verlagsgesellschaft GmbH, Weinheim, pp 353–358

    Google Scholar 

  23. Trijbels JMF, Sengers RCA, Ruitenbeck W, Fischer JC, Bakkeren JAJM, Janssen AJM (1988) Disorders of the mitochondrial respiratory chain: clinical manifestation and diagnostic approach. Eur J Pediatr 148: 92–97

    Article  PubMed  Google Scholar 

  24. Williams SR (1992) In vivo proton spectroscopy. Experimental aspects and potential. In: Diehl P, Fluck E, Günther H, Kosfeld R, Seelig J (eds) NMR basic principles and progress. Vol 28. Springer Verlag, Berlin Heidelberg New York, pp 55–72

    Google Scholar 

  25. Wharton DC, Tzagoloff A (1967) Cytochrome oxidase from beef heart mitochondria. Methods Enzymol 10: 245–250

    Google Scholar 

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Kurlemann, G., Paetzke, I., Möller, H. et al. Therapy of complex I deficiency: Peripheral neuropathy during dichloroacetate therapy. Eur J Pediatr 154, 928–932 (1995). https://doi.org/10.1007/BF01957508

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  • DOI: https://doi.org/10.1007/BF01957508

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