Mitochondrial myopathy and myoclonic epilepsy

Miopatia mitocondrial e epilepsia mioclônica

Walter O. Arruda Luiz F. B. Torres Anne lombes Salvatore Dimauro Belkiss A. Cardoso Hélio A. G. Teive Duilton de Paola Ricardo R. Seixas About the authors

Abstracts

The authors describe a family (mother, son and two daughters) with mitochondrial myopathy. The mother was asymptomatic. Two daughters had lactic acidosis and myoclonic epilepsy, mild dementia, ataxia, weakness and sensory neuropathy. The son suffered one acute hemiplegic episode due to an ischemic infarct in the right temporal region. All the patients studied had hypertension. EEG disclosed photomyoclonic response in the proband patient. Muscle biopsy disclosed ragged-red fibers and abnormal mitochondria by electron microscopy. Biochemical analysis showed a defect of cytochrome C oxidase in mitochondria isolated from skeletal muscle. Several clinical and genetic aspects of the mitochondrial encephalomyopathies are discussed.


Os autores descrevem uma família de raça negra (mãe e três filhos) com miopatia mitocondrial. Duas irmãs tinham acidose láctica concomitante e epilepsia mioclônica. Outros achados observados nos membros mais afetados foram demência, ataxia, fraqueza muscular e neuropatia sensitiva. A mãe era assintomática. Um filho sofreu acidente vascular cerebral isquêmico envolvendo a região temporal direita. Todos os membros da família estudados eram hipertensos. EEG mostrou resposta fotomioclônica na paciente probanda. Biópsia muscular mostrou «ragged-red» fibers e mitocôndrias anormais ao estudo de microscopia eletrônica. Análise bioquímica mostrou um defeito no citocromo C oxidase nas mitocôndrias extraídas do músculo esquelético de uma paciente afetada. Aspectos clínicos e genéticos sobre as encefalomiopatias mitocondriais são discutidos.


Walter O. ArrudaI; Luiz F. B. TorresII; anne lombesIII; Salvatore DimauroIV; Belkiss A. CardosoV; Hélio A. G. TeiveI; Duilton de PaolaVI Ricardo R. SeixasVII

INeurologist

IIPhD, Neuropathologist, Hospital Nossa Senhora das Graças and Hospital de Clínicas, Universidade Federal do Paraná (UFPR)

IIIMD, Postdoctoral Fellowship, H. Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Diseases (HHMCRCMDRD), Columbia College of Physicians and Surgeons, New York

IVProfessor of Neurology, HHMCRCMDRD, Columbia College of Physicians and Surgeons, New York

VMSc, Endocrinologist, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro

VIService of Electroencephalography, Hospital de Clínicas, UFPR

VIINeurophysiologist. Dr. Walter O. Arruda and Belkiss A. Cardoso are in receipt of a CNPq and CAPES grants, respectively

SUMMARY

The authors describe a family (mother, son and two daughters) with mitochondrial myopathy. The mother was asymptomatic. Two daughters had lactic acidosis and myoclonic epilepsy, mild dementia, ataxia, weakness and sensory neuropathy. The son suffered one acute hemiplegic episode due to an ischemic infarct in the right temporal region. All the patients studied had hypertension. EEG disclosed photomyoclonic response in the proband patient. Muscle biopsy disclosed ragged-red fibers and abnormal mitochondria by electron microscopy. Biochemical analysis showed a defect of cytochrome C oxidase in mitochondria isolated from skeletal muscle. Several clinical and genetic aspects of the mitochondrial encephalomyopathies are discussed.

RESUMO

Os autores descrevem uma família de raça negra (mãe e três filhos) com miopatia mitocondrial. Duas irmãs tinham acidose láctica concomitante e epilepsia mioclônica. Outros achados observados nos membros mais afetados foram demência, ataxia, fraqueza muscular e neuropatia sensitiva. A mãe era assintomática. Um filho sofreu acidente vascular cerebral isquêmico envolvendo a região temporal direita. Todos os membros da família estudados eram hipertensos. EEG mostrou resposta fotomioclônica na paciente probanda. Biópsia muscular mostrou «ragged-red» fibers e mitocôndrias anormais ao estudo de microscopia eletrônica. Análise bioquímica mostrou um defeito no citocromo C oxidase nas mitocôndrias extraídas do músculo esquelético de uma paciente afetada. Aspectos clínicos e genéticos sobre as encefalomiopatias mitocondriais são discutidos.

Full text available only in PDF format.

Texto completo disponível apenas em PDF.

Dr. Walter O. Arruda - Unidade de Ciências Neurológicas - Rua Gonçalves Dias 713 - 80240 Curitiba PR - Brasil.

  • 1. Argov Z, Bank WJ, Maris J, Eleff S, Kennaway NG, Olson RE, Chance B - Treatment of mitochondrial myopathy due to complex III deficiency with vitamins K3 and C: a 31P-NMR follow-up study. Ann Neurol 19:598, 1986.
  • 2. Arruda WO, Torres LFB, Teive HAG, Seixas RR, Paola D, Cardoso BA, Paola R, Parolin MKF - Miopatia mitocondrial e epilepsia mioclônica: um estudo familial. Tema livre do XIII Congresso Brasileiro de Neurologia. Arq Neuro-Psiquiat (São Paulo) 46 (Suppl): 145. 1988.
  • 3. Arts W, Scholte H, Bogard J, Kerrebijn KF, Luyt-Houwen IBM - NADH-CoQ reductase deficient myopathy: successful treatment with riboflavin. Lancet 2:581, 1983.
  • 4. Berkovic SF, Andermann F, Carpenter S, Wolfe LS - Progressive myoclonus epilepsies: specific causes and diagnosis. N Engl J Med 315:296, 1986.
  • 5. Berkovic SF, Carpenter S, Karpati G, Andermann F, Andermann E, Shoubrisge E, Arnold D - Cytochrome C oxidase deficiency: a remarkable spectrum of clinical and neuropathological findings in a single family. Neurology 37 (Suppl) :223, 1987.
  • 6. Bradley WG, Tommlinson BE, Hardy M - Further studies of mitochondrial and lipid storage myopathies. J Neurol Sci 35:201, 1978.
  • 7. Byrne E, Dennett X, Trounce I, Burdon J - Mitochondrial myoneuropathy with respiratory failure and myoclonic epilepsy: a case report with biochemical studies. J Neurol Sci 71:273, 1985.
  • 8. D'Agostino AN, Ziter FA, Rallison ML, Bray PF - Familial myopathy with abnormal mitochondria. Arch Neurol 18:388, 1968.
  • 9. DiMauro S, Bunilla E, Zeviani M, Nakagawa M, DeVivo DC - Mitochondrial myopathies. Ann Neurol 17:521, 1985.
  • 10. Dobkin BH, Verity MA - Familial progressive bulbar and spinal muscular atrophy: juvenile onset and late morbidity with ragged-red fibers. Neurology 26:754, 1976.
  • 11. Egger J, Lake BD, Wilson J - Mitochondrial cytopathy: a multisystem disorder with ragged-red fibers on muscle biopsy. Arch Dis Child 56:741, 1981.
  • 12. Egger J, Wilson J - Mitochondrial inheritance in a mitochondrially mediated disease. N Engl J Med 309:142, 1983.
  • 13. Fisher ER, Danowski TS - Mitochondrial myopathy. Am J Clin Pathol 51:619, 1969.
  • 14. Fitzimons RB, Clifton-Bligh P, Wolfenden WH - Mitochondrial myopathy and lactic acidemia with myoclonic epilepsy, ataxia and hypothalamic infertility: a variant of Ramsay-Hunt syndrome? J Neurol Neurosurg Psychiat 44:79, 1981.
  • 15. Fukuhara N, Tokiguchi S, Shirakawa K, Tsubaki T - Myoclonus epilepsy associated with ragged-red fibres (mitochondrial abnormalities): disease entity or a syndrome? J Neurol Sci 47:117, 1980.
  • 16. Fukuhara N - Strokelike episodes in MERRF. Ann Neurol 18:368, 1985.
  • 17. Garcia Silva MT, Aicardi J, Goutierres F, Chevrie JJ - The syndrome of myoclonic epilepsy with ragged-red fibers: report of a case and review of the literature. Neuro-pediatrics 18:200, 1987.
  • 18. Holt IJ, Harding AE, Morgan-Hughes JA - Mitochondrial DNA polymorphism in mitochondrial myopathy. Hum Genet 79:53, 1988.
  • 19. Holt IJ, Harding AE, Morgan-Hughes JA - Deletions of mitochondrial DNA in patients with mitochondrial myopathies. Nature 331:717, 1988.
  • 20. Horwitz SJ, Roessmann U - Kearns-Sayre syndrome with hipoparathyroidism. Ann Neurol 3:513, 1978.
  • 21. Hudgson P, Bradley WG, Jenkinson M - Familial «mitochondrial» myopathy: a myopathy associated with disordered oxidative metabolism in muscle fibres. Part I: Clinical, electrophysiological and pathological findings. J Neurol Sci 16:343, 1972.
  • 22. Julien J, Vital C, Vallat JM, Roger P, Lunel G, Vallat M - Myopathic oculaire avec hypogonadisme primaire: anomalies mitochondriales en ultrastructure. Rev Neurol (Paris) 128:365, 1973.
  • 23. Kenaway NG, Buist RNM, Darley-Usmar VM, Papadimitriou A, DiMauro S, Kelley RI, Capaldi RA, Blank NK, D'Agostino A - Lactic acidosis and mitochondrial myopathy associated with deficiency of several components of complex III of the respiratory chain. Pediatr Res 18:991, 1984.
  • 24. King JO - Progressive myoclonic epilepsy due to Gaucher's disease in an adult. J Neurol Neurosurg Psychiat 38:849, 1975.
  • 25. Kuriyama M, Umezaki H, Fukuda Y, Osame M, Koike K, Tateishi J, Igata A - Mitochondrial encephalomyopathy with lactate-pyruvate elevation and brain infarctions. Neurolgy 34:72, 1984.
  • 26. Lombes A, Mendell JR, Nakase H, Barohn RJ, Bonilla E, Zeviani M, Yates AJ, Omerza J, Gales TL, Nakahara K, Rizzuto R, Engel K, DiMauro S - Myoclonic epilepsy and ragged-red fibers (MERRF) with cytochrome c oxidase deficiency: neuropathological, biochemistry, and molecular genetics. Ann Neurol (in gress).
  • 27. Luft R, Ikkos D, Palmieri G, Ernster L, Afzelius B - A case of severe, hypermetabolism of nonthyroid origin with a defect in the maitenance of mitochondrial respiratory control: a correlated clinical, biochemical, and morphological study. J Clin Invest 41:1776, 1962.
  • 28. Markesbery WR - Lactic acidemia, mitochondrial myopathy, and basal ganglia calcification. Neurology 29:1057, 1979.
  • 29. McLeod JG, Baker WC, Shorey CD, Kerr CB - Mitochondrial myopathy with multisystem abnormalities and normal ocular movements. J Neurol Sci 24:39, 1975.
  • 30. Morgan-Hughes JA, Darveniza P, Kahn SN, Landon DN, Sherratt RM, Land JM, Clark JB - A mitochondrial myopathy characterized by a deficiency in reducible cytochrome b. Brain 100:617, 1977.
  • 31. Morgan-Hughes JA, Hayes DJ, Clark JB, Landon DN, Swash M, Stark RJ, Rudge P - Mitochondrial encephalomyopathies: biochemical studies in two cases revealing defects in the respiratory chain. Brain 105:553, 1982.
  • 32. Mullie MA, Harding AE, Petty RKH, Ikeda H, Morgan-Hughes JA, Sanders MD - The retinal manifestations of mitochondrial myopathy, a study of 22 cases. Arch Ophthalm 103:1825. 1985.
  • 33. Neville HE, Brooke MH, Austin JH - Studies in myoclonus epilepsy (Lafora body form): IV. Skeletal muscle abnormalities. Arch Neurol 30:466, 1974.
  • 34. Olson W, Engel WK, Walsh GO, Einaugler R - Oculocraniosomatic neuromuscular disease with «ragged-red» fibers. Arch Neurol 26:193, 1972.
  • 35. Pavlakis SG, Phillips PC, DiMauro S, DeVivo DC, Rowland LP - Mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes: a distinctitve clinical syndrome. Ann Neurol 16:481, 1984.
  • 36. Peterson PL, Martens ME, Lee CP - Mitochondrial encephalomyopathies. Neurol Clin 6:529, 1988.
  • 37. Petty RKH, Harding AE, Morgan-Hughes JA - The clinical features of mitochondrial myopathy. Brain 109:915. 1986.
  • 38. Riggs JE, Shochet SS, Fakadei AV, Papadimitriou A, DiMauro S, Crosby TW, Gutmann L. Moxley III, RT - Mitochondrial encephalomyopathy with decreased succinate-cytochrome c reductase activity. Neurology 34:48. 1S84.
  • 39. Roger J, Pelisier JF, Dravet C, Bureau-Paillas M, Arnoux M, Larrieu JL - Dégéné-rescence spino-cérébelleuse, atropine optique, épilepsie-myoclonies et myopathie mitochondrials Rev Neurol (Paris) 138:187, 1982.
  • 40. Rosing HS, Hopkins LC, Wallace DC, Epstein CM, Weidenheim K - Maternally inherited mitochondrial myopathy and myoclonic epilepsy. Ann Neurol 17:228, 1985.
  • 41. Rustam H, Hamdi T, Witri S - Progressive familial myoclonus epilepsy. J Neurol Neurosurg Psychiat 38:845, 1975.
  • 42. Sengers RCA, Stadhousers AM, Lakwiik-Vondrovicova E, Kubat K, Ruitenbeek W - Hypertrophic cardiomyopathy associated with a mitochondrial myopathy of voluntary muscles and congenital cataract. Br Heart J 54:543, 1985.
  • 43. Shapira Y, Harel S, Russell A - Mitochondrial encephalomyopathies: a group of neuromuscular disorder with defects in oxidative metabolism. Israel J Med Sci 13:161, 1977.
  • 44. Somerville EH, Olanow CW - Valproic acid: treatment of myoclonus in dyssynergia cerebellaris myoclonica. Arch Neurol 39:527, 1982.
  • 45. Spiro AJ, Moore CL, Prineas JW, Strasberg PM, Rapin I - A cytochrome-related inherited disorder of the nervous system and muscle. Arch Neurol 23:103, 1970.
  • 46. Tatsumi C, Takahashi M, Yorifuii S, Kitagichi M, Tarui S - Mitochondrial encephalomyopathy, ataxia, and sleep apnea. Neurology 37:1429, 1987.
  • 47. Toppet M, Telerman-Toppet N, Szliwowski HB, Vainsel M, Coers C - Oculocraniosomatic neuromuscular disease with hipoparathyroidism. Am J Dis Child 131:437, 1977.
  • 48. Tsairis P, King Engel W, Kark P - Familial myoclonic epilepsy syndrome associated with skeletal muscle mitochondrial abnormalities. Neurology 23:408, 1973.
  • 49. Vilming ST, Dietrichson P, Isachsen MM, Lovvik L, Heiberg A - Late-onset hereditary myopathy with abnormal mitochondria and progressive dementia. Acta Neurol Scand 73:502, 1986.
  • 50. Wallace DL, Zheng X, Lott MT - Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease. Cell 55:601, 1988.
  • 51. Werneck LC, Abdalla H, Lohr A - MELAS (Mitochondrial encephalopathy, lactic acidosis and stroke like episodes). Arq Neuro-Psiquiat (São Paulo) 45:288, 1987.
  • 52. Tamamoto T, Beppu H, Tsubaki T - Mitochondrial encephalomyopathy: fluctuating symptoms and CT. Neurology 34:1456, 1984.
  • 53. Yannikas C, McLeod JG, Pollard JD, Baverstock J - Peripheral neuropathy associated with mitochondrial myopathy. Ann Neurol 20:249, 1986.
  • 54. Zeviani M, Moraes CT, DiMauro S, Nakase H, Bonilla E, Schon EA, Rowland LP - Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology 38:1339, 1988.
  • 55. Zeviani M, Bonilla E, DeVivo DC, DiMauro S - Mitochondrial diseases. Neurol Clin 7:123, 1989.
  • 56. Zinn AB, Kerr DS, Hoppel CL - Fumarase deficiency: a new cause of mitochondrial encephalomyopathy. N Engl J Med 315:469, 1986.

  • Mitochondrial myopathy and myoclonic epilepsy
    Miopatia mitocondrial e epilepsia mioclônica

Publication Dates

  • Publication in this collection
    25 May 2011
  • Date of issue
    Mar 1990
Academia Brasileira de Neurologia - ABNEURO R. Vergueiro, 1353 sl.1404 - Ed. Top Towers Offices Torre Norte, 04101-000 São Paulo SP Brazil, Tel.: +55 11 5084-9463 | +55 11 5083-3876 - São Paulo - SP - Brazil
E-mail: revista.arquivos@abneuro.org