Deficiência muscular de carnitina: relato de 8 casos com estudo clínico, eletromiográfico, histoquímico e bioquímico muscular

Werneck, Lineu Cesar; Di Mauro, Salvatore

doi:10.1590/S0004-282X1985000300007

Resumos

São relatados os casos de 8 pacientes, sendo 7 do sexo masculino, cuja idade variou entre 5 dias e 64 anos. Sete pacientes apresentavam diminuição da força muscular e todos apresentavam, nas biópsias musculares, acúmulo de lipídios. Os sintomas iniciaram nos primeiros dias de vida em três pacientes, na infância em dois, na idade adulta em dois; um dos casos apresentava-se assinto-mático aos 64 anos de idade (heterozigoto?). Em graus variáveis os pacientes apresentavam dificuldades na deglutição, hipotonia, atrofia muscular, dificuldades na mastigação, parestesias em membros inferiores, hepatomegalia e esplenome-galia. Cinco casos tinham história familiar e um relatava recorrências dos sintomas. Todos apresentavam aumento dos enzimas séricos, principalmente da creatinoquinase. A eletromiografia foi compatível a envolvimento muscular primário em um caso, desenervação em dois e neuromiopático em dois, não tendo sido realizada em três casos. Na biópsia muscular, em todos os casos, além do acúmulo de lipídios, ocorriam: componente de desenervação em 4, miopa-tia crônica em 4, atrofia de fibras do tipo II em um. Em dois casos, as alterações histológicas eram sugestivas de atrofia espinhal infantil. Um dos casos, possivelmente pertencente à forma sistêmica de deficiência de carnitina, possuía importante envolvimento miocárdico, vindo a falecer. São discutidos aspectos clínicos, metabólicos e terapêuticos das deficiências musculares de carnitina.

We describe 8 patients with muscle carnitine deficiency, 7 males and 1 female, varying in age from 5 days to 64 years. Seven had decreased muscle strength and all had increased lipids droplets in the muscle biopsy. The symptoms began in the first days of life in three cases, in childhood in two, in adult life in two, while one case was free of symptoms at age 64 (heterozygote?). Some patients had difficulty chewing, dysphagia, hypotonia and splenomegaly; one patient had a fluctuating clinical course. All had elevated serum enzymes, mainly creatine-kinase. The electromyogram showed primary muscle involvement in one case, denervation in two, "mixed" features in two and was not done in three. The muscle biopsy, beside lipid storage, showed denervation in four, chronic myopathy in four and type II fiber atrophy in one. In two cases, histological findings suggested infantile spinal muscle atrophy. One patient appeared to have a systemic form of carnitine deficiency, with severe myocardial involvement and died of heart failure before treatment was initiated. A discussion about clinical findings, metabolism and therapeutic aspects of muscle carnitine deficiency is made.

Deficiência muscular de carnitina: relato de 8 casos com estudo clínico, eletromiográfico, histoquímico e bioquímico muscular

Muscle carnitine deficiency: report of 8 cases, with clinical, electromyographic, histochemical and biochemical studies

Lineu Cesar Werneck^I; Salvatore Di Mauro^II

^IProfessor Assistente de Neurologia

^IIProfessor de Neurologia

RESUMO

São relatados os casos de 8 pacientes, sendo 7 do sexo masculino, cuja idade variou entre 5 dias e 64 anos. Sete pacientes apresentavam diminuição da força muscular e todos apresentavam, nas biópsias musculares, acúmulo de lipídios. Os sintomas iniciaram nos primeiros dias de vida em três pacientes, na infância em dois, na idade adulta em dois; um dos casos apresentava-se assinto-mático aos 64 anos de idade (heterozigoto?). Em graus variáveis os pacientes apresentavam dificuldades na deglutição, hipotonia, atrofia muscular, dificuldades na mastigação, parestesias em membros inferiores, hepatomegalia e esplenome-galia. Cinco casos tinham história familiar e um relatava recorrências dos sintomas. Todos apresentavam aumento dos enzimas séricos, principalmente da creatinoquinase. A eletromiografia foi compatível a envolvimento muscular primário em um caso, desenervação em dois e neuromiopático em dois, não tendo sido realizada em três casos. Na biópsia muscular, em todos os casos, além do acúmulo de lipídios, ocorriam: componente de desenervação em 4, miopa-tia crônica em 4, atrofia de fibras do tipo II em um. Em dois casos, as alterações histológicas eram sugestivas de atrofia espinhal infantil. Um dos casos, possivelmente pertencente à forma sistêmica de deficiência de carnitina, possuía importante envolvimento miocárdico, vindo a falecer. São discutidos aspectos clínicos, metabólicos e terapêuticos das deficiências musculares de carnitina.

SUMMARY

We describe 8 patients with muscle carnitine deficiency, 7 males and 1 female, varying in age from 5 days to 64 years. Seven had decreased muscle strength and all had increased lipids droplets in the muscle biopsy. The symptoms began in the first days of life in three cases, in childhood in two, in adult life in two, while one case was free of symptoms at age 64 (heterozygote?). Some patients had difficulty chewing, dysphagia, hypotonia and splenomegaly; one patient had a fluctuating clinical course. All had elevated serum enzymes, mainly creatine-kinase. The electromyogram showed primary muscle involvement in one case, denervation in two, "mixed" features in two and was not done in three. The muscle biopsy, beside lipid storage, showed denervation in four, chronic myopathy in four and type II fiber atrophy in one. In two cases, histological findings suggested infantile spinal muscle atrophy. One patient appeared to have a systemic form of carnitine deficiency, with severe myocardial involvement and died of heart failure before treatment was initiated. A discussion about clinical findings, metabolism and therapeutic aspects of muscle carnitine deficiency is made.

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Trabalho realizado na Especialidade de Neurologia do Departamento de Clínica Médica da Universidade Federal do Paraná, Curitiba e The Houston Merritt Clinical Research Center for Muscular Dystrophy and Related Disorders, Columbia University, College of Physicians and Surgeons, New York.

Agradecimento: Agradecemos ao Dr. Cláudio G. Naylor, do Hospital dos Servidores Públicos do Rio de Janeiro, que nos permitiu estudar o caso 4 e ao Dr. Mauro Pedro da Cunha, Maringá, PR, a referência do caso 2.

Hospital de Clínicas da Universidade Federal do Paraná, Departamento de Clinica Médica, Especialidade de Neurologia - Ruu General Carneiro nº 181, 13ª andar - 80.000, Curitiba, PR - Brasil.

1. ANGELINI, C; LUCKE, S. & CANTARUTTI, F. - Carnitine deficiency of skeletal muscle: Report of a treated case. Neurology 25:533, 1976.
2. BERTORINI, T.; YEH, Y-Y.; TREVISAN, C.; STADLAN, E.; SABESIN, S. & DI MAURO, S. - Carnitine palmityl transferase deficiency: myoglobinuria and respiratory failure. Neurology 30:263, 1980.
3. BORUM, P.R.; BROQUIST, H.P. & ROELOFS, R.I. - Muscle carnitine levels in neuromuscular disease. J. neurol. Sci. 34:279, 1977.
4. BOUDIN, G.; MIKOL, J.; GUILLARD, H. & ENGEL, A.G. - Fatal systemic carnitine deficiency with lipid storage in skeletal muscle, heart, liver and kidney. J. neurol. Sci. 30:313, 1976.
5. BRADLEY, W.C.; HUDGSON, P.; GARDNER-MEDWIN, D. & WALTON, J.N. - Myopathy associated with abnormal lipid metabolism in skeletal muscle. Lancet 1:495, 1969.
6. BRADLEY, W.C.; TOMLISON, B.E. & HARDY, M. - Further studies of mitochondrial and lipid storage myopathies. J. neurol. Sci. 35:201, 1978.
7. CORNELIO, F.; DI DONATO, S.; PELUCHETTI, D.; BIZZI, A.; BERTAGNOLIO, B.; D'ANGELO, A. & WIESMANN, U. - Fatal case of lipid storage myopathy with carnitine deficiency. J. Neurol. Neurosurg. Psychiat. 40:170, 1977.
8. DI DONATO. S.; CORNELIO, F.; STORCHI, G. & RIMOLDI, M. - Hepatic ketogenesis and muscle carnitine deficiency. Neurology 29:780, 1979.
9. DI MAURO, S.; TREVISAN, C. & HAYS, A. - Disorders of lipid metabolism in muscle. Muscle & Nerve 3:369, 1980.
10. ENGEL, A.G. & ANGELINI, C. - Carnitine deficiency of human skeletal muscle with associated lipid storage myopathy: a new syndrome. Science 179:899, 1973.
11. ENGEL, A.G.; BANKER, B.W. & EIBEN, R.M. - Carnitine deficiency: clinical, morphological and biochemical observation in a fatal case. J. Neurol. Neurosurg. Psychiat. 40:313, 1977.
12. ENGEL, A.G.; REBOUCHE, C.J.; WILSON, D.M.; GLASGOW, A.M.; ROMSHE, C.A. & CRUSE, R.P. - Primary systemic carnitine deficiency. II. Renal handling of carnitine. Neurology 31:819, 1981.
13. ENGEL, A.G. & SIEKERT, R.G. - Lipid storage myopathy responsive to prednisone. Arch. Neurol. 27:174, 1972.
14. ENGEL, W.K.; VICK, N.A.; GLUECK, J. & LEVY, R.I. - A skeletal muscle disorder associated with intermittent symptoms and a possible defect of lipid metabolism. N. Engl. J. Med. 282:697, 1970.
15. GRIGGS, R.C.; PANDYA, S.; MOXLEY, R.T.; FORBES, G.; VANDYKE, D.H. & PEARCE, F.J. - Treatment of myopathic carnitine deficiency: quantitation of response to prednisone and carnitine. Trans. amer. neurol. Assoc. 106:199, 1981.
16. HART, Z.H.; CHANG, C-H; DI MAURO, S.; FAROOKI, W. & AYYAR, R. - Muscle carnitine deficiency and fatal cardiomyopathy. Neurology 28:147, 1978.
17. ISAACS, H.; HEFFRON, J.J.A.; BADENHORST, N. & PICKERING, A. - Weakness associated with the pathological presence of lipid in skeletal muscle: A detailed study of a patient with carnitine deficiency. J. Neurol. Neurosurg. Psychiat. 39:1114, 1976.
18. KARPATI, G.; CARPENTER, S.; ENGEL., A.G.; WATTERS, G.; ALLEN, J. ROTHMAN, S.; KLASSEN, G. & NAMER, O.A. - The syndrome of systemic carnitine deficiency. Clinical, morphological, biochemical and pathophysiologic features. Neurology 25:14, 1975.
19. MARKESBERY, W.R.; McQUILLEN, M.P.; PROCOPIS, P.G.; HARRISON, A.R. & ENGEL, A.G. - Muscle carnitine deficiency. Association with lipid myopathy, vacuolar neuropathy and vacuolated leukocytes. Arch. Neurol. 31:320, 1974.
20. MARTYN, C; JELLINNE; E.H. & WEBB, J.N. - Lipid storage myopathy: successfull treatment with propranolol. Brit. med. J. 282:1997, 1981.
21. REBOUCHE, C.J. & ENGEL, A.G. - Significance of renal gama-butyrobetaíne hidroxilase for carnitine biosynthesis in man. J. biol. Chem. 255:8700, 1980.
22. REBOUCHE, C.J. & ENGEL, A.G. - Primary systemic carnitine deficiency. I. Carnitine biosynthesis. Neurology 31:813, 1981.
23. REBOUCHE, C.J. & ENGEL, A.G. - Carnitine metabolism and deficiency syndromes. Mayo Clin. Proc. 58:533, 1983.
24. SCARLATO, G.; PELLEGRINI, G.; CERRI, C; MEOLA, G. & VEICSTEINAS, A. - The syndrome of carnitine deficiency: Morphological and metabolic correlations in two cases. Canadian J. neurol. Sci. 5:205, 1978.
25 SMYTH, D.P.L. ; LAKE, B.D.; MacDERMOT, J. & WILSON, J. - Inborns error of carnitine metabolism («Carnitine deficiency») in man. Lancet 1:1198, 1975.
26. TRIPP, M.E.; PETERS, H.A.; GILBERT, E.F.; ARYA, S.; HODACH, R.J. & SHUG, A.L. - Systemic carnitine deficiency presenting as familial endocardial fibroelastosis. A treatable cardiomyopathy. N. Engl. J. Med. 305:385, 1981.
27. VANDYKE, D.H.; GRIGGS, R.C.; MARKESBERY, W. & Dl MAURO, S. - Hereditary carnitine deficiency of muscle. Neurology 25:154, 1975.
28. WABER, L.J.; VALLE, D.; NEILL, C; DI MAURO, S. & SHUG, A. - Systemic carnitine deficiency presenting as a familial cardiomyopathy: a treatable defect in carnitine transport. J. Pediat. 101:700, 1982.
29. WERNECK, L.C. - O valor da biópsia muscular em neurologia. Análise de 290 exames a fresco e pela histoquímica. Rev. bras. Clin. Terap. 10: edição especial, 1981.
30. WERNECK, L.C.; BOER, C.A.A.; PAPADIMITRIOU, A. & Dl MAURO, S. - Miopatia por deficiência de carnitina-palmitil-transferase. Relato de 2 casos com dosagens enzimáticas no tecido muscular. Arq. Neuro-Psiquiat. (São Paulo) 41:377, 1983.
31. WILLNER, J.H.; Dl MAURO, S.; EASTWOOD, A.; HAYS, A.; ROOHI, F. & LOVELACE, R. - Muscle carnitine deficiency-genetic heterogenicity. J. neurol. Sci. 41:235, 1979.

Datas de Publicação

Publicação nesta coleção
13 Ago 2012
Data do Fascículo
Set 1985

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

[1] 1. ANGELINI, C; LUCKE, S. & CANTARUTTI, F. - Carnitine deficiency of skeletal muscle: Report of a treated case. Neurology 25:533, 1976.

[2] 2. BERTORINI, T.; YEH, Y-Y.; TREVISAN, C.; STADLAN, E.; SABESIN, S. & DI MAURO, S. - Carnitine palmityl transferase deficiency: myoglobinuria and respiratory failure. Neurology 30:263, 1980.

[3] 3. BORUM, P.R.; BROQUIST, H.P. & ROELOFS, R.I. - Muscle carnitine levels in neuromuscular disease. J. neurol. Sci. 34:279, 1977.

[4] 4. BOUDIN, G.; MIKOL, J.; GUILLARD, H. & ENGEL, A.G. - Fatal systemic carnitine deficiency with lipid storage in skeletal muscle, heart, liver and kidney. J. neurol. Sci. 30:313, 1976.

[5] 5. BRADLEY, W.C.; HUDGSON, P.; GARDNER-MEDWIN, D. & WALTON, J.N. - Myopathy associated with abnormal lipid metabolism in skeletal muscle. Lancet 1:495, 1969.

[6] 6. BRADLEY, W.C.; TOMLISON, B.E. & HARDY, M. - Further studies of mitochondrial and lipid storage myopathies. J. neurol. Sci. 35:201, 1978.

[7] 7. CORNELIO, F.; DI DONATO, S.; PELUCHETTI, D.; BIZZI, A.; BERTAGNOLIO, B.; D'ANGELO, A. & WIESMANN, U. - Fatal case of lipid storage myopathy with carnitine deficiency. J. Neurol. Neurosurg. Psychiat. 40:170, 1977.

[8] 8. DI DONATO. S.; CORNELIO, F.; STORCHI, G. & RIMOLDI, M. - Hepatic ketogenesis and muscle carnitine deficiency. Neurology 29:780, 1979.

[9] 9. DI MAURO, S.; TREVISAN, C. & HAYS, A. - Disorders of lipid metabolism in muscle. Muscle & Nerve 3:369, 1980.

[10] 10. ENGEL, A.G. & ANGELINI, C. - Carnitine deficiency of human skeletal muscle with associated lipid storage myopathy: a new syndrome. Science 179:899, 1973.

[11] 11. ENGEL, A.G.; BANKER, B.W. & EIBEN, R.M. - Carnitine deficiency: clinical, morphological and biochemical observation in a fatal case. J. Neurol. Neurosurg. Psychiat. 40:313, 1977.

[12] 12. ENGEL, A.G.; REBOUCHE, C.J.; WILSON, D.M.; GLASGOW, A.M.; ROMSHE, C.A. & CRUSE, R.P. - Primary systemic carnitine deficiency. II. Renal handling of carnitine. Neurology 31:819, 1981.

[13] 13. ENGEL, A.G. & SIEKERT, R.G. - Lipid storage myopathy responsive to prednisone. Arch. Neurol. 27:174, 1972.

[14] 14. ENGEL, W.K.; VICK, N.A.; GLUECK, J. & LEVY, R.I. - A skeletal muscle disorder associated with intermittent symptoms and a possible defect of lipid metabolism. N. Engl. J. Med. 282:697, 1970.

[15] 15. GRIGGS, R.C.; PANDYA, S.; MOXLEY, R.T.; FORBES, G.; VANDYKE, D.H. & PEARCE, F.J. - Treatment of myopathic carnitine deficiency: quantitation of response to prednisone and carnitine. Trans. amer. neurol. Assoc. 106:199, 1981.

[16] 16. HART, Z.H.; CHANG, C-H; DI MAURO, S.; FAROOKI, W. & AYYAR, R. - Muscle carnitine deficiency and fatal cardiomyopathy. Neurology 28:147, 1978.

[17] 17. ISAACS, H.; HEFFRON, J.J.A.; BADENHORST, N. & PICKERING, A. - Weakness associated with the pathological presence of lipid in skeletal muscle: A detailed study of a patient with carnitine deficiency. J. Neurol. Neurosurg. Psychiat. 39:1114, 1976.

[18] 18. KARPATI, G.; CARPENTER, S.; ENGEL., A.G.; WATTERS, G.; ALLEN, J. ROTHMAN, S.; KLASSEN, G. & NAMER, O.A. - The syndrome of systemic carnitine deficiency. Clinical, morphological, biochemical and pathophysiologic features. Neurology 25:14, 1975.

[19] 19. MARKESBERY, W.R.; McQUILLEN, M.P.; PROCOPIS, P.G.; HARRISON, A.R. & ENGEL, A.G. - Muscle carnitine deficiency. Association with lipid myopathy, vacuolar neuropathy and vacuolated leukocytes. Arch. Neurol. 31:320, 1974.

[20] 20. MARTYN, C; JELLINNE; E.H. & WEBB, J.N. - Lipid storage myopathy: successfull treatment with propranolol. Brit. med. J. 282:1997, 1981.

[21] 21. REBOUCHE, C.J. & ENGEL, A.G. - Significance of renal gama-butyrobetaíne hidroxilase for carnitine biosynthesis in man. J. biol. Chem. 255:8700, 1980.

[22] 22. REBOUCHE, C.J. & ENGEL, A.G. - Primary systemic carnitine deficiency. I. Carnitine biosynthesis. Neurology 31:813, 1981.

[23] 23. REBOUCHE, C.J. & ENGEL, A.G. - Carnitine metabolism and deficiency syndromes. Mayo Clin. Proc. 58:533, 1983.

[24] 24. SCARLATO, G.; PELLEGRINI, G.; CERRI, C; MEOLA, G. & VEICSTEINAS, A. - The syndrome of carnitine deficiency: Morphological and metabolic correlations in two cases. Canadian J. neurol. Sci. 5:205, 1978.

[25] 25 SMYTH, D.P.L. ; LAKE, B.D.; MacDERMOT, J. & WILSON, J. - Inborns error of carnitine metabolism («Carnitine deficiency») in man. Lancet 1:1198, 1975.

[26] 26. TRIPP, M.E.; PETERS, H.A.; GILBERT, E.F.; ARYA, S.; HODACH, R.J. & SHUG, A.L. - Systemic carnitine deficiency presenting as familial endocardial fibroelastosis. A treatable cardiomyopathy. N. Engl. J. Med. 305:385, 1981.

[27] 27. VANDYKE, D.H.; GRIGGS, R.C.; MARKESBERY, W. & Dl MAURO, S. - Hereditary carnitine deficiency of muscle. Neurology 25:154, 1975.

[28] 28. WABER, L.J.; VALLE, D.; NEILL, C; DI MAURO, S. & SHUG, A. - Systemic carnitine deficiency presenting as a familial cardiomyopathy: a treatable defect in carnitine transport. J. Pediat. 101:700, 1982.

[29] 29. WERNECK, L.C. - O valor da biópsia muscular em neurologia. Análise de 290 exames a fresco e pela histoquímica. Rev. bras. Clin. Terap. 10: edição especial, 1981.

[30] 30. WERNECK, L.C.; BOER, C.A.A.; PAPADIMITRIOU, A. & Dl MAURO, S. - Miopatia por deficiência de carnitina-palmitil-transferase. Relato de 2 casos com dosagens enzimáticas no tecido muscular. Arq. Neuro-Psiquiat. (São Paulo) 41:377, 1983.

[31] 31. WILLNER, J.H.; Dl MAURO, S.; EASTWOOD, A.; HAYS, A.; ROOHI, F. & LOVELACE, R. - Muscle carnitine deficiency-genetic heterogenicity. J. neurol. Sci. 41:235, 1979.