Summary
In skeletal muscle from a patient with a mitochondrial myopathy and muscular carnitine deficiency, histochemical analysis demonstrated that mitochondrial ATPase showed activation with loss of latency even before addition of the uncoupler dinitrophenol (DNP). According to combined histochemical and biochemical studies by Meijer and Vloedman (1980), this finding indicates loosely coupled oxidative phosphorylation. After the addition of DNP the reaction intensity was markedly increased, but there were scattered enzyme-deficient fibres in which some residual activity was shown by ultracytochemistry. No defect in mitochondrial enzymes was found in biochemical studies.
The enzyme histochemical changes and carnitine deficiency are probably both secondary to an unknown mitochondrial defect. Both the carnitine deficiency and the mitochondrial myopathy remained unchanged following long-term carnitine substitution therapy despite clinical improvement.
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References
Angelini C (1976) Lipid storage myopathies. J Neurol 214:1–11
Barth PG, Scholte HR, Berden JA, Van der Klei-Van Moorsei, Luyt-Houwen IEM, Van’t Veer-Korthof ET, Van der Harten JJ, Sobotka-Plojhar MA (1983) An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes. J Neurol SCI 62:327–355
Bradley WG, Tomlinson BE, Hardy M (1978) Further studies of mitochondrial and lipid storage myopathies. J Neurol Sci 35:201–210
Bremer J (1983) Carnitine — metabolism and functions. Physiological reviews. 63:1420–1480
Busch MFM, Scholte MR, Arts WF, Luyt-Houwen IEM (1981) A mitochondrial myopathy with a respiratory chain defect and carnitine deficiency. In: Busch HFM, Jennekens FGI, Scholte MR (eds) Mitochondria and muscular diseases. Mefar, Beesterzwaag, pp 207–211
Busch HFM, Scholte HR, Luyt-Houwen IEM, Arts WFM (1984) A mitochondrial myopathy with a deficiency of NADH-CoQ reductase activity in a mother and son. Third int Symposium on inborn errors of metabolism in humans. Karger, Basel, ISBN3-8055-3894-4, 39–40 [Abstr]
Carroll JE, Brooke MH, De Vivo DC, Shurmate JB, Kratz R, Ringel SP, Hagberg JM (1980) Carnitine deficiency: Lack of response to carnitine therapy. Neurology 30:618–626
Chapoy PR, Angelini C, Brown WJ, Stiff JE, Shug AL, Cederbaum SD (1980) Systemic carnitine deficiency a treatable inherited lipid-storage disease presenting as Reye’s syndrome. N Eng J Med 303:1389–1394
Cornelio F, Di Donato S, Peluchetti D, Bizzi A, Bertagnolio B, D’Angelo A, Wiesmann U (1977) Fatal cases of lipid storage myopathy with carnitine dificiency. J Neurol Neurosurg Psychiatry 40:170–178
Di Donato S, Cornelio F, Balestrini MR, Bertagnolio B, Peluchetti D (1978) Mitochondrialipid-glycogen myopathy, hyperlactacidemia, and carnitine deficiency. Neurology 28:1110–1116
Di Donato S, Peluchetti M, Rimoldi M, Mora M, Garavaglia B, Finocchiaro G (1984) Systemic carnitine deficiency: clinical biochemical and morphological cure with 1-carnitine. Neurology 34:157–162
Di Mauro S, Bonilla E, Lee CP, Schotland DL, Scarpa A, Conn H, Chance B (1976) Luffs disease. Further biochemical and ultrastructural studies of skeletal muscle in the second case. J Neurol Sci 27:217–232
Di Mauro S, Trevisan C, Hays A (1980a) Disorders of lipid metabolism in muscle. Muscle Nerve 3:369–388
Di Mauro S, Mendell JR, Sahenk Z, Bachmann D, Scarpa A, Scofield RM, Rainer C (1980b) Fatal infantile mitochondrial myopathy and renal dysfunction due to cytochrome-c-oxidase deficiency. Neurology 30:795–804
Engel AG (1980) Possible causes and effects of carnitine deficiency in man. In: Frenkel RA, McGarry JD (eds) Carnitine biosynthesis, metabolism and functions. Academic Press, New York, pp 271–285
Ernster L, Ikkos D, Luft R (1959) Enzymatic activities of human skeletal muscle mitochondria a tool in clinical metabolic research. Nature 184:1851–1854
Hart ZH, Chang ChD, Di Mauro S, Farooki Q, Ayyar R (1978) Muscle carnitine deficiency and fatal cardiomyopathy. Neurology 28:147–151
Haydar NA, Conn HL, Afifï A, Wakid N, Ballas S, Fawaz K (1971) Severe hypermetabolism with primary abnormality of skeletal muscle mitochondria. Ann Int Med 74:548–588
Heiman-Patterson TD, Bonilla E, Di Mauro S, Foreman J, Schotland DL (1982) Cytochromec-oxidase deficiency in a floppy infant. Neurology 32:898–900
Jerusalem F, Angelini C, Engel AG, Groover RV (1973) Mitochondria lipid glycogen disease of muscle. Arch Neurol 29:162–169
Karpati G, Carpenter S, Engel AG, Watters G, Allen J, Rothman S, Klassen G, Marner O (1975) The syndrome of systemic carnitine deficiency. Neurology 25:16–24
Luft R, Ikkos D, Palmieri G, Ernster L, Afzelius B (1962) A case of severe hypermetabolism of non-thyroid origin with a defect in the maintenance of mitochondrial respiratory control. A correlated clinical, biochemical and morphological study. J Clin Invest 41:1776–1804
Meijer AEFH (1972) Morphologie, Histochemie and Biochemie mitochondrialer Skelettmuskelkrankheiten. Acta Histochem [Suppl] 7:333–334
Meijer AEFH (1977) Skeletal muscle disease with disordered oxidative phosphorylation in the isolated muscle mitochondria. Cell Mol Biol 23:257–265
Meijer AEFH (1981) The histochemical detection of loosely coupled mitochondria in biopsies of skeletal muscles. In: Busch HFM, Jennekens FGI, Scholte HR (eds) Mitochondria and muscular diseases. Mefar, Beetsterzwaag, pp 71–76
Meijer AEFH (1983) The histochemical demonstration of loosely coupled mitochondria in human skeletal muscle. Histochem J 15:331–335
Meijer AEFH, Vloedman AHT (1980) The histochemical characterization of the coupling state of skeletal muscle mitochondria. Histochemistry 69:217–232
Meijer AE:FH, Scholte HR, Busch HFM (1984) Zur histochemischen Kennzeichnung und der möglichen Bedeutung von Skelettmuskelmitochondrien mit einem Defekt der oxidativen Phosphorylierung. 4. Int Myologie-Kolloquium Jena, April 1984
Morgan-Hughes JA (1982) Mitochondrial myopathies. In: Mastaglia FL, Walton F (eds) Churchill-Livingstone, Endinburgh, London, pp 309–339
Morgan-Hughes JA, Landon DN (1983) Mitochondrial respiratory chain deficiency in man. In: Cerri C (eds) Mitochondrial pathology in muscle diseases G Scarlato. Piccin medical books, Padua, pp 19–37
Müller-Höcker J, Pongratz D, Deufel Th, Trijbels JMF, Endres W, Hübner G (1983) Fatal lipid storage myopathy with deficiency of cytochrome-c-oxidase and carnitine. Virchows Arch [Pathol Anat] 399:11–23
Müller-Höcker J, Walther JU, Bise K, Pongratz D, Hübner G (1984) Mitochondrial myopathy with loosely coupled oxidative phosphorylation in a case of Zellweger syndrome. Virchows Arch [Cell Pathol] 45:125–138
Pongratz D, Hübner G, Deufel Th, Wieland O, Pongrratz E, Liphardt R (1979) Klinische morphologische und biochemische Befunde bei Carnitinmangelmyopathien. Klin Wochenschr 57:927–936
Prockop LD, Engel WK, Shug AL (1983) Nearly fatal muscle carnitine deficiency with full recovery after replacement therapy. Neurology 33:1629–1631
Rebouche Ch, Engel AG (1983) Carnitine metabolism and deficiency syndromes. Mayo Clin Proc 58:533–540
Rimoldi M, Bottacchi E, Rossi L, Cornelio F, Uziel G, Di Donato S (1982) Cytochrome-coxidase deficiency in muscles of a floppy infant without mitochondrial myopathy. J Neurol 227:201–207
Scarlato G, Pellegrini G, Cerri C, Meola G, Veicsteinas A (1978) The syndrome of carnitine deficiency: Morphological and metabolic correlations in two cases. J Can Sci Neurol 5:205–213
Schölte HR, Busch HFM, Barth PG, Beekman RP, Berden JA, Duran M, Luyt-Houwen IEM, Przyrembel H, Roth B, De Vries S (1983) Carnitine deficiency and mitochondrial respiratory chain blockade. In: Scarlato G, Cerri C (eds) Mitochondrial pathology in muscle diseases. Piccin Medical books, Padua, pp 215–228
Sengers RCA, Fischer JC, Trijbels JMF, Ruitenbeek W, Stadhouders AM, ter Laak HF, Jaspar JH (1983) A mitochondrial myopathy with a defective respiratory chain and carnitine deficiency. Eur J Pediatr 140:332–337
Sengers RCA, Trijbels JMF, Bakkeren JAJM, Ruitenbeek W, Fischer JC, Janssen AJM, Stadhouders AM, Laak HJ (1984) Deficiency of cytochrome-b and aa3 in muscle from a floppy infant with cytochrome-c-oxidase deficiency. Eur J Pediatr 141:178–180
Waber LJ, Valle D, Neill A, Di Mauro S, Shug A (1982) Carnitine deficiency presenting as familial cardiomyopathy: A treatable defect in carnitine transport. J Pediatr 1001:700–705
Willner J Di Mauro S, Eastwood A, Hays A, Roohi F, Lovelace R (1979) Muscle carnitine deficiency. J Neurol Sci 41:235–246
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Dedicated to Professor Max Eder on the occasion of his 60th birthday
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Müller-Höcker, J., Paetzke, I., Pongratz, D. et al. Mitochondrial myopathy with diffuse activation and focal deficiency of mitochondrial ATPase and carnitine deficiency. Virchows Archiv B Cell Pathol 48, 185–196 (1985). https://doi.org/10.1007/BF02890127
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DOI: https://doi.org/10.1007/BF02890127