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.
Similar content being viewed by others
References
Angelini C (1976) Lipid storage myopathies. J Neurol 214:1–11
Böhmer T, Bergrem H, Eiklid K (1978) Carnitine deficiency induced during intermittend haemodialysis for renal failure. Lancet 1:126–128
Borst P, Loos JA, Christ EJ, Slater EC (1962) Uncoupling activity of long-chain fatty acids. Biochim Biophys Acta 62:509–518
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
Brownell AKW, Engel AG (1978) Experimental lipid storage myopathy. A quantitative ultra-structural and biochemical study. J Neurol Sci 35:31–41
Carrier HN, Berthillier G (1980) Carnitine levels in normal children and adults and in patients with diseased muscle. Muscle Nerve 3:326–334
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 of 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 deficiency. J Neurol Neurosurg. Psychiatry 40:170–178
Deufel Th (1981) Klinisch-biochemische Untersuchung zum Carnitinstoffwechsel des Menschen und zur Diagnostik von Carnitinmangel-Syndromen. Dissertation, München Dezember
Di Donato S, Cornelio F, Balestrini MR, Bertagnolio B, Peluchetti D (1978) Mitochondria-lipid-glycogen myopathy, hyperlactacidemia, and carnitine deficiency. Neurology 28:1110–1116
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
Di Mauro S, Trevisan C, Hays A (1980b) Disorders of lipid metabolism in muscle. Muscle Nerve 3:369–388
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
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
Engel AG (1966) Thyrotoxic and corticosteroid-induced myopathies. Proc Mayo Clin 41:785–796
Engel WK (1970) Selective and nonselective susceptibility of muscle fiber types. Arch Neurol 22:97–117
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
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
Esiri M, Bower B, Ross B (1979) Fatal lipid storage myopathy in an infant. J Neurol Sci 41:93–100
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
Gulotta F, Payk ThR, Solbach A (1974) Sudanophile (mitochondriale) Myopathie. Z Neurol 206:309–326
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
Hart ZH, Chang ChD, Di Mauro S, Farooki Q, Ayyar R (1978) Muscle carnitine deficiency and fatal cardiomyopathy. Neurology 28:147–151
Herzog V, Fahimi HD (1974) The effect of glutaraldehyde on catalase. J C Biol 60:303–311
Jerusalem F, Spiess E, Baumgartner G (1975) Lipid storage myopathy with normal carnitine levels. J Neurol Sci 24:273–282
Kamieniecka Z, Schmalbruch H (1980) Neuromuscular disorders with abnormal muscle mitochondria. Int Rev Cytol 65:321–357
Karnovsky ML (1979) A case of metabolic mimicry. N Engl J Med 301:1442–1443
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
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
Monnens L, Gabreels F, Willems J (1975) A metabolic myopathy associated with chronic lactic acidemia, growth failure, and nerve deafness. J Pediatr 86:983
Penn D, Schmidt-Sommerfeld E, Wolf H (1980) Carnitine deficiency in premature infants receiving total parenteral nutrition. Early Human Development 4/1:23–24
Penn D, Schmidt-Sommerfeld E, Pascu F (1981) Decreased tissue carnitine concentrations in newborn infants receiving total parenteral nutrition. J Pediatr 98:76–78
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
Prineas J, Ng RCY (1967) Ultrastructural features of intracellular lipid in normal human muscle. Neurology 17:1092–1098
Prineas J, Hall R, Barwick DD, Watson AJ (1968) Myopathy associated with pigmentation following adrenalectomy for Cushing Syndrome. Quart J Med 37:63–77
Rebouche CJ, Engel AG (1980) In vitro analysis of hepatic carnitine biosynthesis in human systemic carnitine deficiency. Clin Chim Acta 106:295–300
Rudman D, Sewell CW, Ansley JD (1977) Deficiency of carnitine in cachectic, cirrhotic patients. J Clin Invest 60:716–723
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
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
Scarlato G, Meola G, Scarpini E, Cerri C (1978b) Muscular carnitine synthesis and palmitate metabolism in vitro. J Neurol 218:149–156
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
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
Scholte HR, Stinis JT, Jennekens FG (1978) Low carnitine levels in serum of pregnant women. N Engl J Med 299:1079–1080
Schröder JM (1982) Pathologie der Muskulatur. Springer, Berlin Heidelberg New York
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
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
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
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
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
Walter GF (1981) Neuromuskuläre Mitochondriopathie. Gustav Fischer Stuttgart, New York
Ware AJ, Burton WC, McGarry JD, Markes JF, Weinberg AG (1978) Systemic carnitine deficiency. J Pediatr 93:959–964
Willner J, Di Mauro S, Eastwood A, Hays A, Roohi F, Lovelace R (1979) Muscle carnitine deficiency. J Neurol Sci 41:235–246
Zborowski J, Wojtczak KL (1963) Induction of swelling of liver mitochondria by fatty acids of various chain length. Biochim Biophys acta 70:596
Author information
Authors and Affiliations
Rights 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
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00666215