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Paradoxical effect of sodium valproate that aggravates epilepsy of MELAS in a patient with A3243G mutation of the mitochondrial DNA

  • Case Report
  • Published:
Central European Journal of Medicine

Abstract

Epilepsy is an associated feature of patients with the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). A substitution at nucleotide position 3243 A>G of the mitochondrial DNA is the most common mutation encountered both in Caucasians and in Chinese/Taiwanese. We herein report a 38-year-old man with A3243G mutation of the mitochondrial DNA whom developed MELAS. The manifestation of his focal motor epilepsy was aggravated by use of sodium valproate (VPA). The mechanism of this paradoxical effect is proposed.

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References

  1. J.M. Shoffner: “Maternal inheritance and the evaluation of oxidative phosphorylation diseases”, Lancet, Vol. 348, (1996), pp. 1283–1288.

    Article  PubMed  CAS  Google Scholar 

  2. P.F. Chinnery, N. Howell, R.N. Lightowlers and D.M. Turnbull: “Molecular pathology of MELAS and MERRF: The relationship between mutation load and clinical phenotypes”, Brain, Vol. 120, (1997), pp. 1713–1721.

    Article  PubMed  Google Scholar 

  3. S. Dimauro and G. Davidzon: “Mitochondrial DNA and disease”, Ann. Med., Vol. 37, (2005), pp. 222–232.

    Article  PubMed  CAS  Google Scholar 

  4. S. DiMauro: “Mitochondrial diseases”, Biochim. Biophys. Acta, Vol. 1658, (2004), pp. 80–88.

    Article  PubMed  CAS  Google Scholar 

  5. S.G.. Pavlakis, P.C. Phillips, S. DiMauro, D.C. DeVivo and L.P. Rowlan: “Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctive clinical syndrome”, Ann. Neurol., Vol. 16, (1984), pp. 481–488.

    Article  PubMed  CAS  Google Scholar 

  6. P. Thajeb, D.F. Dai, M.F. Chiang and W.C. Shyu: “Genotype-phenotype correlation of maternally inherited disorders due to mutations of the mitochondrial DNA”, Taiwanese J. Obstet. Gynecol., Vol. 45(3), (2006), pp. 201–207.

    PubMed  Google Scholar 

  7. C.C. Huang, R.S. Chen, C.M. Chen, H.S. Wang, C.C. Lee, C.Y. Pang, H.S. Hsu, H.C. Lee and Y.H. Wei: “MELAS syndrome with mitochondrial tRNALeu(UUR) gene mutation in a Chinese family”, J. Neurol. Neurosury. Psychiatry, Vol. 57, (1994), pp. 586–589.

    Article  CAS  Google Scholar 

  8. C.W. Liou, C.C. Huang, E.C. Chee, Y.J. Jong, J.L Tsai, C.Y. Pang, H.C. Lee and Y.H. Wei: “MELAS syndrome: correlation between clinical features and molecular genetic analysis”, Acta Neurol. Scand., Vol. 90, (1994), pp. 354–359.

    Article  PubMed  CAS  Google Scholar 

  9. W. Fang, C.C. Huang, C.C. Lee, S.Y. Cheng, C.Y. Pang and Y.H. Wei: “Ophthalmologic manifestations in MELAS syndrome”, Arch. Neurol., Vol. 50, (1993), pp. 977–980.

    PubMed  CAS  Google Scholar 

  10. P. Thajeb, M.C. Wu, B.F. Shih, C.Y. Tzen, M.F. Chiang and R.Y. Yuan: “Brain SPECT studies in patients with A3243G mutation of the mitochondrial DNA”, Ann. N. Y. Acad. Sci., Vol. 1042, (2005), pp. 48–54.

    Article  PubMed  CAS  Google Scholar 

  11. C.Y. Tzen CY, P. Thajeb, T.Y. Wu and S.C. Chen: “MELAS with point mutations involving tRNALeu (A3243G) and tRNAGlu(14693G)”, Muscle Nerve, Vol. 28, (2003), pp. 575–581.

    Article  PubMed  CAS  Google Scholar 

  12. Y. Zhang, J.F. Li, F.Y. Wang and C.X. Li: “The study of A3243G and G13513A mitochondria DNA point mutation in patients with cerebral infarction”, Chin. Med. J. (Beijing), Vol. 114, (2001), pp. 129–135.

    Google Scholar 

  13. U. Altrup, H. Reith and E.J. Speckmann: “Effects of valproate in a model nervous system (buccal ganglia of Helix pomatia): II. Epileptogenic actions”, Epilepsia, Vol. 33, (1992), pp. 753–759.

    Article  PubMed  CAS  Google Scholar 

  14. B. Chabrol, J. Mancini, D. Chretien, P. Rustin, A. Munnich and N. Pinsard: “Valproate-induced hepatic failure in a case of cytochrome c oxidase deficiency”, Eur. J. Pediatr., Vol. 153, (1994), pp. 133–135.

    PubMed  CAS  Google Scholar 

  15. S. Ponchaut, F. Van Hoof and K. Veitch: “Cytochrome c oxidase depletion is the cause of the deficient mitochondrial respiration induced by chronic valproate administration”, Biochem. Pharmacol., Vol. 43, (1992), pp. 644–647.

    Article  PubMed  CAS  Google Scholar 

  16. S. Ponchaut, F. Van Hoof and K. Veitch: “Valproate and cytochrome c oxidase deficiency”, Eur. J. Pediatr., Vol. 154, (1995), p. 79.

    Article  PubMed  CAS  Google Scholar 

  17. C.W. Lam, C.H. Lau, J.C. Williams, Y.W. Chan and L.J. Wong: “Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) triggered by valproate therapy”, Eur. J. Pediatr., Vol. 156, (1997), pp. 562–564.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Neurology and Medical Research, Mackay Memorial Hospital, Taipei City, Taiwan, ROC

    Yi-Min Chen, Chih-Ming Lin & Peterus Thajeb

  2. School of Medicine, National Yang-Ming University, Taipei City, Taiwan, ROC

    Peterus Thajeb

  3. Taipei Medical University, Taipei, Taiwan, ROC

    Peterus Thajeb

Authors
  1. Yi-Min Chen
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  2. Chih-Ming Lin
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  3. Peterus Thajeb
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Chen, YM., Lin, CM. & Thajeb, P. Paradoxical effect of sodium valproate that aggravates epilepsy of MELAS in a patient with A3243G mutation of the mitochondrial DNA. cent.eur.j.med 2, 103–107 (2007). https://doi.org/10.2478/s11536-007-0007-5

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  • DOI: https://doi.org/10.2478/s11536-007-0007-5

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