Mitochondrial dysfunction in myasthenia gravis: report of a case

Marchiori, Paulo E.; Levy, J. A.; Lusvarghi, Mary S. Carvalho-Alegro E. S.; Tsanaclis, Ana M.; Assis, J. Lamartine de; Scaff, M.

doi:10.1590/S0004-282X1989000300018

Abstracts

The case of an 11-year-old boy with external ophtalmoparesia, tetraparesia and bilateral eyelid ptosis is reported. He was 7-years-old when first symptoms appeared. Anticholinesterasic drugs were used. He was submitted to muscle biopsy. The results of histochemistry analysis showed storage of granulous material at the subsarcolemmal region of muscle fibers by SDH. Increase in the number of mitochondria with electron dense bodies was found at electron microscopy. Anticholinesterasic drugs administration was interrupted and consequently he got worse, and bouts of dyspnea occurred. Due to this worsening anticholinesterasic agents were reintroduced together with prednisone, and he improved. Due to clinical and histological expressions we think it is possible that morphological mitochondrial alterations may occur also in myasthenia gravis.

É relatado o caso de um paciente de 11 anos de idade com oftalmoparesia extrínseca, ptose palpebral bilateral e tetraparesia desde os 7 anos de idade. A concentração de anticorpos contra receptor de acetilcolina por radioimunoensaio foi 0,6 nM/1; a pesquisa de anticorpos contra músculo estriado foi negativa. Exame eletromiográfico revelou decremento de 26,1%. Foi tratado com brometo de piridostigmina na dose de 60 mg/d. Submetido a biópsia de tecido muscular estriado (biceps braquial esquerdo) com avaliações por métodos histoquímicos e microscopia eletrônica, que revelaram: acúmulos de mitocôndrias na região subsarcolemal na coloração pela SDH; aumento da concentração de mitocôndrias e corpúsculos eletrodensos à microscopia eletrônica; esses achados são sugestivos de miopatia mitocondrial. Em conseqüência da interrupção das drogas anticolinesterásicas ocorreu piora das manifestações deficitárias, disfagia e dispnéia. Reintroduzidos os anticolinesterásicos, associados a imunossupressão com corticosteróides, houve melhora e retomada pelo paciente de suas atividades habituais. Destarte, é discutido o caráter inespecífico das alterações morfogenéticas e disfunções de mitocôndrias em outras patologias neuromusculares, incluindo a miastenia grave, como neste, caso em particular.

Mitochondrial dysfunction in myasthenia gravis: report of a case

Disfunção mitocondrial na miastenia crave: relato de caso

Paulo E. Marchiori; J. A. Levy; Mary S. Carvalho-Alegro E. S. Lusvarghi; Ana M. Tsanaclis; J. Lamartine de Assis; M. Scaff

Division of Neurology, Hospital das Clínicas (HC), Faculty ef Medicine, University of São Paulo (FMUSP)

SUMMARY

The case of an 11-year-old boy with external ophtalmoparesia, tetraparesia and bilateral eyelid ptosis is reported. He was 7-years-old when first symptoms appeared. Anticholinesterasic drugs were used. He was submitted to muscle biopsy. The results of histochemistry analysis showed storage of granulous material at the subsarcolemmal region of muscle fibers by SDH. Increase in the number of mitochondria with electron dense bodies was found at electron microscopy. Anticholinesterasic drugs administration was interrupted and consequently he got worse, and bouts of dyspnea occurred. Due to this worsening anticholinesterasic agents were reintroduced together with prednisone, and he improved. Due to clinical and histological expressions we think it is possible that morphological mitochondrial alterations may occur also in myasthenia gravis.

RESUMO

É relatado o caso de um paciente de 11 anos de idade com oftalmoparesia extrínseca, ptose palpebral bilateral e tetraparesia desde os 7 anos de idade. A concentração de anticorpos contra receptor de acetilcolina por radioimunoensaio foi 0,6 nM/1; a pesquisa de anticorpos contra músculo estriado foi negativa. Exame eletromiográfico revelou decremento de 26,1%. Foi tratado com brometo de piridostigmina na dose de 60 mg/d. Submetido a biópsia de tecido muscular estriado (biceps braquial esquerdo) com avaliações por métodos histoquímicos e microscopia eletrônica, que revelaram: acúmulos de mitocôndrias na região subsarcolemal na coloração pela SDH; aumento da concentração de mitocôndrias e corpúsculos eletrodensos à microscopia eletrônica; esses achados são sugestivos de miopatia mitocondrial. Em conseqüência da interrupção das drogas anticolinesterásicas ocorreu piora das manifestações deficitárias, disfagia e dispnéia. Reintroduzidos os anticolinesterásicos, associados a imunossupressão com corticosteróides, houve melhora e retomada pelo paciente de suas atividades habituais. Destarte, é discutido o caráter inespecífico das alterações morfogenéticas e disfunções de mitocôndrias em outras patologias neuromusculares, incluindo a miastenia grave, como neste, caso em particular.

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Clínica Neurológica, Hospital das Clínicas - Caixa Postal 3461 - 01051 São Paulo SP - Brasil.

1. Arnold DL, Taylor DJ, Radda GK - Investigation of human mitochondrial myopathies by phosphorus magnetic resonance spectroscopy. Ann Neurol 18: 189, 1985.
2. Chance B, Williams GR - The respiratory chain and oxidative phosphorylation. Advanc Enzymol 17: 65, 1956-7.
3. DiMauro S, Bonilla E, Zeviani M, Nakagawa M, DeVivo DC - Mitochondrial myopathies. Ann Neurol 17: 521, 1985.
4. Fine PEM - Mitochondrial inheritance and disease. Lancet 2: 659, 1978.
5. Kamieniecka Z, Schmalbruch H - Neuromuscular disorders with abnormal muscle mitochondria. Int Rev Cytol 65: 321, 1980.
6. Kamieniecka Z, Schmalbruch H - Neuromuscular disorders with abnormal muscle mitochondria. Int Rev Cytol 65: 321, 1980.
7. Land JM, Clark JB - Mitochondrial myopathies. Biochern Soc Trans 7: 231, 1969.
8. Lousa M, Gobernado JM, Gosalvez M - Mitochondrial function in myasthenia gravis. Europ Neurol 22: 53, 1983.
9. Mechler F, Mastaglia FL, Serena M, Jenkison M, Johnson MA, Fawcett PRW, Hudgson P, Walton JN - Mitochondrial myopathies: a clinico-pathological study of cases with and without extra-ocular muscle involvement. Aust NZ J Med 16: 185, 1986.
10. Petty RKH, Harding AE, Morgan-Hughes HA - The clinical features of mitochondrial myopathy. Brain 109: 915, 1986.
11. Shah AJ, Sahgal V, Muschler G, Subramani V, Singh H - Morphogenesis or the mitochondrial alterations in muscle diseases. J Neurol Sci 55: 25, 1982.
12. Schotland DL, DiMauro S, Bonilla E, Scarpa A, Lee CP - Neuromuscular disorder associated with a defect in mitochondrial energy supply. Arch Neurol 33: 475, 1976.
13. Tzagoloff A, Myers AM - Genetics of mitochondrial biogenesis. Ann Rev Biochem 55: 249, 19S6.
14. van Wijngaarden GK, Bethlem J, Meijer AEFH, Hülsmann WC, Feltjkamp CA - Skeletal muscle disease with abnormal mitochondria. Brain 90: 577, 1967.

Publication Dates

Publication in this collection
06 June 2011
Date of issue
Sept 1989

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Arnold DL, Taylor DJ, Radda GK - Investigation of human mitochondrial myopathies by phosphorus magnetic resonance spectroscopy. Ann Neurol 18: 189, 1985.

[2] 2. Chance B, Williams GR - The respiratory chain and oxidative phosphorylation. Advanc Enzymol 17: 65, 1956-7.

[3] 3. DiMauro S, Bonilla E, Zeviani M, Nakagawa M, DeVivo DC - Mitochondrial myopathies. Ann Neurol 17: 521, 1985.

[4] 4. Fine PEM - Mitochondrial inheritance and disease. Lancet 2: 659, 1978.

[5] 5. Kamieniecka Z, Schmalbruch H - Neuromuscular disorders with abnormal muscle mitochondria. Int Rev Cytol 65: 321, 1980.

[6] 6. Kamieniecka Z, Schmalbruch H - Neuromuscular disorders with abnormal muscle mitochondria. Int Rev Cytol 65: 321, 1980.

[7] 7. Land JM, Clark JB - Mitochondrial myopathies. Biochern Soc Trans 7: 231, 1969.

[8] 8. Lousa M, Gobernado JM, Gosalvez M - Mitochondrial function in myasthenia gravis. Europ Neurol 22: 53, 1983.

[9] 9. Mechler F, Mastaglia FL, Serena M, Jenkison M, Johnson MA, Fawcett PRW, Hudgson P, Walton JN - Mitochondrial myopathies: a clinico-pathological study of cases with and without extra-ocular muscle involvement. Aust NZ J Med 16: 185, 1986.

[10] 10. Petty RKH, Harding AE, Morgan-Hughes HA - The clinical features of mitochondrial myopathy. Brain 109: 915, 1986.

[11] 11. Shah AJ, Sahgal V, Muschler G, Subramani V, Singh H - Morphogenesis or the mitochondrial alterations in muscle diseases. J Neurol Sci 55: 25, 1982.

[12] 12. Schotland DL, DiMauro S, Bonilla E, Scarpa A, Lee CP - Neuromuscular disorder associated with a defect in mitochondrial energy supply. Arch Neurol 33: 475, 1976.

[13] 13. Tzagoloff A, Myers AM - Genetics of mitochondrial biogenesis. Ann Rev Biochem 55: 249, 19S6.

[14] 14. van Wijngaarden GK, Bethlem J, Meijer AEFH, Hülsmann WC, Feltjkamp CA - Skeletal muscle disease with abnormal mitochondria. Brain 90: 577, 1967.