Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Fatal lipid storage myopathy with deficiency of cytochrome-c-oxidase and carnitine

A contribution to the combined cytochemical-finestructural identification of cytochrome-c-oxidase in longterm frozen muscle

  • 38 Accesses

  • 67 Citations

Summary

Two newborn female siblings fell ill with apathy, failure of suckling and a generalized progressive muscular hypotonia. Death occured at the age of 7 weeks, obviously caused by impairment of respiratory musculature. Biochemical studies in one child revealed carnitine deficiency especially in skeletal muscle; hepatic encephalopathy was absent. Both children had a generalized hyperaminoaciduria, an unusual finding in primary carnitine deficiency.

Besides fatty metamorphosis of the liver, bilateral hydroureters and tubular calcifications of both kidneys, morphological studies showed a generalized lipid storage myopathy which predominated in Type-I-fibres and was accentuated in the muscles of the neck. Enzymehistochemical electron microscopy in longterm frozen muscle demonstrated that cytochrome-c-oxidase activity was absent not only in myopathic but also in most of the morphological unchanged muscle fibres. Only some fibres and endothelial cells displayed normal activity of mitochondria. Biochemically no cytochrome aa3 (cytochrome-c-oxidase) could be found in skeletal muscle; cytochrome b was almost undetectable. - In newborns with fatal lipid storage myopathy and carnitine deficiency it seems necessary to look for additional defects in the respiratory chain. Enzyme histochemical electron microscopy is a sensitive method in identifying cytochrome-c-oxidase even after a 12 months period of storage.

This is a preview of subscription content, log in to check access.

References

  1. Angelini C (1976) Lipid storage myopathies. J Neurol 214:1–11

  2. Böhmer T, Bergrem H, Eiklid K (1978) Carnitine deficiency induced during intermittend haemodialysis for renal failure. Lancet 1:126–128

  3. Borst P, Loos JA, Christ EJ, Slater EC (1962) Uncoupling activity of long-chain fatty acids. Biochim Biophys Acta 62:509–518

  4. Boudin G, Mikol J, Guillard A., Engel AG (1976) Fatal systemic carnitine deficiency with lipid storage in skeletal muscle, heart, liver and kidney. J Neurol Sci 30:313–325

  5. Brownell AKW, Engel AG (1978) Experimental lipid storage myopathy. A quantitative ultra-structural and biochemical study. J Neurol Sci 35:31–41

  6. Carrier HN, Berthillier G (1980) Carnitine levels in normal children and adults and in patients with diseased muscle. Muscle Nerve 3:326–334

  7. 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

  8. 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 of Med 303:1389–1394

  9. 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 deficiency. J Neurol Neurosurg. Psychiatry 40:170–178

  10. Deufel Th (1981) Klinisch-biochemische Untersuchung zum Carnitinstoffwechsel des Menschen und zur Diagnostik von Carnitinmangel-Syndromen. Dissertation, München Dezember

  11. Di Donato S, Cornelio F, Balestrini MR, Bertagnolio B, Peluchetti D (1978) Mitochondria-lipid-glycogen myopathy, hyperlactacidemia, and carnitine deficiency. Neurology 28:1110–1116

  12. Di Mauro S, Mendell JR, Sahenk Z, Bachman D, Scarpa A, Scofield RM, Rainer C (1980a) Fatal infantile mytochondrial myopathy and renal dysfunction due to cytochrome-c-oxidase deficiency. Neurology 30:795–804

  13. Di Mauro S, Trevisan C, Hays A (1980b) Disorders of lipid metabolism in muscle. Muscle Nerve 3:369–388

  14. Dusheiko G, Kew MC, Joffe BI, Lewin JR, Mantagos S, Tanaka K (1979) Recurrent hypoglycemia associated with glutaric aciduria type II in an adult. N Eng J Med 301:1405–1409

  15. Endres W, Müller-Höcker J, vd Ende A, Schutgens RBH, Biese K, Hübner G, Wadman SK (1981) Cerebro-hepato-renal syndrome of Zellweger: Absence of liver peroxisomes, hypocatalasia and renal excretion of pipecolic and trihydroxycoprostanoid acid. Eur J Pediatr 135:331, Abstr

  16. Engel AG (1966) Thyrotoxic and corticosteroid-induced myopathies. Proc Mayo Clin 41:785–796

  17. Engel WK (1970) Selective and nonselective susceptibility of muscle fiber types. Arch Neurol 22:97–117

  18. Engel AG, Banker BQ, Eiben RM (1977) Carnitine deficiency: clinical, morphological, and biochemical observations in a fatal case. J Neurol Neurosurg Psychiatry 40:313–322

  19. Engel AG (1980) Possible causes and effects of carnitine deficiency in man. In: Frenke RA, McGarry JD (eds) Carnitine biosynthesis, metabolism and functions, Academic Press New York, pp 271–285

  20. Esiri M, Bower B, Ross B (1979) Fatal lipid storage myopathy in an infant. J Neurol Sci 41:93–100

  21. Goldfischer S, Moore CL, Johnson AB, Spiro AJ, Valsamis MP, Wisniewski HK, Ritch RH, Norton WT, Rapin J, Gartner LM (1973) Peroxisomal and mitochondrial defects in the cerebro-hepato-renal syndrome. Science 182:62–64

  22. Gulotta F, Payk ThR, Solbach A (1974) Sudanophile (mitochondriale) Myopathie. Z Neurol 206:309–326

  23. Harriman DGG, Reed R (1972) The incidence of lipid droplets in human skeletal muscle in neuromuscular disorders: A histochemical, electron-microscopic and freeze-etch study. J Pathol 106:1–24

  24. Hart ZH, Chang ChD, Di Mauro S, Farooki Q, Ayyar R (1978) Muscle carnitine deficiency and fatal cardiomyopathy. Neurology 28:147–151

  25. Herzog V, Fahimi HD (1974) The effect of glutaraldehyde on catalase. J C Biol 60:303–311

  26. Jerusalem F, Spiess E, Baumgartner G (1975) Lipid storage myopathy with normal carnitine levels. J Neurol Sci 24:273–282

  27. Kamieniecka Z, Schmalbruch H (1980) Neuromuscular disorders with abnormal muscle mitochondria. Int Rev Cytol 65:321–357

  28. Karnovsky ML (1979) A case of metabolic mimicry. N Engl J Med 301:1442–1443

  29. Karpati G, Carpenter S, Engel AG, Watters G, Allen J, Rothman S, Klassen G, Mamer O (1975) The syndrome of systemic carnitine deficiency. Neurol 25:16–24

  30. Miranda A, Di Mauro S, Eastwood A, Hays A, Johnson WG, Olarte M, Whitlock R, Mayeux R, Rowland LP (1979) Lipid storage myopathy, ichthyosis and steatorrhea. Muscle Nerve 2:1–13

  31. Monnens L, Gabreels F, Willems J (1975) A metabolic myopathy associated with chronic lactic acidemia, growth failure, and nerve deafness. J Pediatr 86:983

  32. Penn D, Schmidt-Sommerfeld E, Wolf H (1980) Carnitine deficiency in premature infants receiving total parenteral nutrition. Early Human Development 4/1:23–24

  33. Penn D, Schmidt-Sommerfeld E, Pascu F (1981) Decreased tissue carnitine concentrations in newborn infants receiving total parenteral nutrition. J Pediatr 98:76–78

  34. Pongratz D, Hübner G, Deufel Th, Wieland O, Pongratz E, Liphardt R (1979) Klinische, morphologische und biochemische Befunde bei Carnitinmangelmyopathien. Klin Wochenschr 57:927–936

  35. Prineas J, Ng RCY (1967) Ultrastructural features of intracellular lipid in normal human muscle. Neurology 17:1092–1098

  36. Prineas J, Hall R, Barwick DD, Watson AJ (1968) Myopathy associated with pigmentation following adrenalectomy for Cushing Syndrome. Quart J Med 37:63–77

  37. Rebouche CJ, Engel AG (1980) In vitro analysis of hepatic carnitine biosynthesis in human systemic carnitine deficiency. Clin Chim Acta 106:295–300

  38. Rudman D, Sewell CW, Ansley JD (1977) Deficiency of carnitine in cachectic, cirrhotic patients. J Clin Invest 60:716–723

  39. Sengers RCA, Bakkeren JA, Trijbels JM, Stadhouders AM, Egberink GJ, ter Laak HJ, Jaspar HJ (1980) Successful carnitine treatment in a non-carnitine deficient lipid storage myopathy. Eur J Pediatr 135, 205–209

  40. Scarlato G, Pellegrini G, Cerri C, Meola G, Veicsteinas A (1978a) The syndrome of carnitine deficiency: Morphological and metabolic correlations in two cases. J Can Sci Neurol 5:205–213

  41. Scarlato G, Meola G, Scarpini E, Cerri C (1978b) Muscular carnitine synthesis and palmitate metabolism in vitro. J Neurol 218:149–156

  42. Scholte HR, Meijer AE, van Wijngaarden GK, Leenders KL (1979a) Familial carnitine deficiency. A fatal case and subclinical state in a sister. J Neurol Sci 42:87–101

  43. Scholte HR, Jennekens FG, Bouvy JJ (1979 b) Carnitine palmityltransferase II deficiency with normal carnitine palmityltransferase I in skeletal muscle and leukocytes. J Neurol Sci 40:39–51

  44. Scholte HR, Stinis JT, Jennekens FG (1978) Low carnitine levels in serum of pregnant women. N Engl J Med 299:1079–1080

  45. Schröder JM (1982) Pathologie der Muskulatur. Springer, Berlin Heidelberg New York

  46. Slavin G, Wills EJ, Richmond JE, Chanarin I, Andrews T, Stewart G (1975) Morphological features in a neutral lipid storage disease. J Clin Pathol 28:701–710

  47. Soslau G, Nass MMK (1971) Effects of ethidium bromide on the cytochrome content and ultrastructure of L cell mitochondria. J Cell Biol 51:514–524

  48. Tripp ME, Katcher ML, Peters HA, Gilbert EF, Arya S, Hodach J, Shug AL (1981) Systemic carnitine deficiency presenting as familial endocardial fibroelastosis. N Engl J Med 305:385–390

  49. Van Biervliet JP, Bruinvis L, Ketting D, De Bree PK, vd Heiden C, Wadman SK, Willems JL, Bookelman H, v Haelst U, Monnens LA (1977) Hereditary mitochondrial myopathy with lactic acidemia, a De Toni-Fanconi-Debre syndrome, and a defective respiratory chain in voluntary striated muscles. Pediatric Res 11:1088–1092

  50. Versmold HT, Bremer H J, Herzog V, Siegel G, v Bassewitz DB, Irle U, v Voss H, Lombeck J, Brauser B (1977) A metabolic disorders similar to Zellweger syndrome with hepatic acatalasia and absence of peroxisomes, altered content and redox state of cytochromes, and infantile cirrhosis with hemosiderosis. Eur J Pediatr 124:261–275

  51. Walter GF (1981) Neuromuskuläre Mitochondriopathie. Gustav Fischer Stuttgart, New York

  52. Ware AJ, Burton WC, McGarry JD, Markes JF, Weinberg AG (1978) Systemic carnitine deficiency. J Pediatr 93:959–964

  53. Willner J, Di Mauro S, Eastwood A, Hays A, Roohi F, Lovelace R (1979) Muscle carnitine deficiency. J Neurol Sci 41:235–246

  54. Zborowski J, Wojtczak KL (1963) Induction of swelling of liver mitochondria by fatty acids of various chain length. Biochim Biophys acta 70:596

Download references

Author information

Correspondence to J. Müller-Höcker.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Müller-Höcker, J., Pongratz, D., Deufel, T. et al. Fatal lipid storage myopathy with deficiency of cytochrome-c-oxidase and carnitine. Vichows Archiv A Pathol Anat 399, 11–23 (1982). https://doi.org/10.1007/BF00666215

Download citation

Key words

  • Lipid storage myopathy
  • Carnitine deficiency
  • Mitochondrial myopathy
  • Respiratory chain
  • Cytochrome-c-oxidase
  • Autopsy