Abstract
Current knowledge of the metabolic role, biosynthesis, cellular uptake, excretion and turnover of carnitine is reviewed. The clinical spectrum and possible aetiology of the primary muscle and primary systemic carnitine deficiency syndromes are considered and the various genetic defects of intermediary metabolism which can give rise to secondary carnitine deficiency are indicated.
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Allen, R. J., DiMauro, S. and Coulter, D. L. Kearns-Sayre syndrome (KSS): a possible disorder of folate and carnitine metabolism (abstract).Pediatr. Res. 17 (1983) 286A
Allen, R. J., Hansch, D. B. and Wu, H. L. Hypocarnitinaemia in disorders of organic acid metabolism (letter to the editor).Lancet 2 (1982) 500–501
Allen, R. J., Wong, P., Rothenberg, S. P., DiMauro, S. and Headington, J. T. Progressive neonatal leukoencephalo-myopathy due to absent methylenetetrahydrofolate reductase, responsive to treatment.Ann. Neurol. 8 (1980) 211 (Abstr.)
Angelini, C., Govoni, E., Bragaglia, M. M. and Vergani, L. Carnitine deficiency: acute postpartum crisis.Ann. Neurol. 4 (1978) 558–561
Bieber, L. L., Emaus, R., Valkner, K. and Farrell, S. Possible functions of short-chain and medium-chain carnitine acyltransferases.Fed. Proc. 41 (1982) 2858–2862
Böhles, H., Richter, K., Wagner-Thiessen, E. and Schäfer, H. Decreased serum carnitine in valproate induced Reye syndrome.Eur. J. Pediatr. 139 (1982) 185–186
Bohmer, T., Bergrem, H. and Eiklid, K. Carnitine deficiency induced during intermittent haemodialysis for renal failure.Lancet 1 (1978) 126–128
Bohmer, T., Eiklid, K. and Jonsen, J. Carnitine uptake into human heart cells in culture.Biochim. Biophys. Acta 465 (1977) 627–633
Borum, P. R., Broquist, H. P. and Roelofs, R. I. Muscle carnitine levels in neuromuscular disease.J. Neurol. Sci. 34 (1977) 279–286
Bremer, J. Carnitine precursors in the rat.Biochim. Biophys. Acta 57 (1962) 327–335
Brucher, J. M., Tassin, S., Walter, G. F., Scholte, H. B. and deBarsy, Th. Myopathic carnitine deficiency. Clinical, morphologic and biochemical findings in three cases. In Busch, H. F. M., Jennekens, F. G. I. and Scholte, H. R. ( eds.)Mitochondria and Muscle Disease, Beetsterzwaag, The Netherlands, 1981, pp. 199–205
Busch, H. F. M., Scholte, H. R., Arts, W. F. and Luyt-Houwen, I. E. M. A mitochondrial myopathy with a respiratory chain defect and carnitine deficiency. In Busch, H. F. M., Jennekens, F. G. I. and Scholte, H. R. (eds.)Mitochondria and Muscle Disease, Beetsterzwaag, The Netherlands, 1981, pp. 207–211
Cantrell, C. R. and Borum, P. R. Identification of a cardiac carnitine binding protein.J. Biol. Chem. 257 (1982) 10599–10604
Carrier, H. N. and Berthillier, G. Carnitine levels in normal children and adults and in patients with diseased muscle.Muscle Nerve 3 (1980) 326–324
Chapoy, P. R., Angelini, C., Brown, W. J., Stiff, J. E., Shug, A. L. and Cederbaum, S. D. Systemic carnitine deficiency — a treatable inherited lipid-storage disease presenting as Reye’s syndrome.N. Engl. J. Med. 303 (1980) 1389–1394
Choi, Y. R., Fogle, P. J., Clarke, P. R. H. and Bieber, L. L. Quantitation of water-soluble acylcarnitines and carnitine acyltransferases in rat tissues.J. Biol. Chem. 252 (1977) 7930–7931
Christiansen, R. Z. and Bremer, J. Active transport of butyrobetaine and carnitine into isolated liver cells.Biochim. Biophys. Acta 448 (1976) 562–577
Cornelio, F., DiDonato, S., Peluchetti, D., Rimoldi, M., Daniel, S., Testa, D. and Mora, M. Heterogeneity of carnitine deficiency. Clinicopathologic aspects of eight cases.Perspect. Inher. Metab. Dis. 3 (1979) 129–150
Coudé, F. X., Ogier, H., Carrier, H, Berthillier, G., Charpentier, C, Pham Dinh, D., Aicardi, J. and Saudubray, J. M. Myopathy in methylmalonic acidemia: a new secondary carnitine deficiency syndrome (abstract). InAbstracts of Free Communications, Fifth International Congress on Neuromuscular Diseases, 1982
DiDonato, S., Rimoldi, M., Cornelio, F., Botacchi, E. and Giunta, A. Evidence for autosomal recessive inheritance in systemic carnitine deficiency.Ann. Neurol. 11 (1981) 190–192
Dunn, W. A., Aronson, N. N. Jr. and Englard, S. The effects of 1-amino-d-proline on the production of carnitine from exogenous protein-bound trimethyllysine by the perfused rat liver.J. Biol. Chem. 257 (1982) 7948–7951
Dusheiko, G., Kew, M. C., Joffe, B. I., Lewin, J. R., Mantagos, S. and Tanaka, K. Recurrent hypoglycemia associated with glutaric aciduria type II in an adult.N. Engl. J. Med. 301 (1979) 1405–1409
Engel, A. G. Possible causes and effects of carnitine deficiency in man. In Frenkel, R. A. and McGarry, J. D. (eds.)Carnitine Biosynthesis, Metabolism, and Functions, Academic Press, New York, 1980, pp. 271–285
Engel, A. G. and Angelini, C. Carnitine deficiency of human skeletal muscle with associated lipid storage myopathy: a new syndrome.Science 179 (1973) 899–902
Engel, A. G., Angelini, C. and Nelson, R. A. Identification of carnitine deficiency as a cause of human lipid storage myopathy.Excerpta Medica International Congress Series No. 333 (1974) 601–60617
Engel, A. G. and Rebouche, C. J. Pathogenetic mechanisms in human carnitine deficiency syndromes. In Schotland, D. L. (ed.)Disorders of the Motor Unit, Wiley, New York, 1982, pp. 643–656
Engel, A. G., Rebouche, C. J., Wilson, D. M., Glasgow, A. M., Romshe, C. A. and Cruse, R. P. Primary systemic carnitine deficiency. II Renal handling of carnitine.Neurology (NY) 31 (1981) 819–825
Felig, P. Amino acid metabolism in man.Ann. Rev. Biochem. 44 (1975) 933–955
Fritz, I. B. The metabolic conseq uences of the effects of carnitine on long-chain fatty acid oxidation. In Gran, F. C. (ed.)Cellular Compartmentalization and Control of Fatty Acid Metabolism, Academic Press, New York, 1968, pp. 39–63
Glasgow, A. M., Eng, G. and Engel, A. G. Systemic carnitine deficiency simulating recurrent Reye syndrome.J. Pediatr. 92 (1980) 889–891
Hale, D. E., Coates, P. M., Stanley, C. A., Cortner, J. A. and Hall, C. L. Long-chain acyl CoA dehydrogenase deficiency.Pediatr. Res. 17 (1983) 290A (Abstr.)
Hayes, D. J., Summers, B. A., Morgan-Hughes, J. A. and Clark, J. B. A combined deficiency of muscle carnitine and mitochondrial ATPase activity in a patient with multisystem disease partially responsive to oral carnitine (abstract). InAbstracts of Free Communications, Fifth International Congress on Neuromuscular Diseases, 1982
Henderson, L. M., Nelson, P. J. and Henderson, L. Mammalian enzymes of trimethyllysine conversion to trimethylaminobutyrate.Fed. Proc. 41 (1982) 2843–2847
Hoppel, C. L. Carnitine and carnitine palmitoyltransferase in fatty acid oxidation and ketosis.Fed. Proc. 41 (1982) 2853–2857
Huth, P. J. and Shug, A. L. Properties of carnitine transport in rat kidney cortex slices.Biochim. Biophys. Acta 602 (1980) 621–634
Karpati, G., Carpenter, S., Engel, A. G., Watters, G., Allen, J., Rothman, S., Klassen, G. and Mammer, O. A. The syndrome of systemic carnitine deficiency: clinical, morphologic, biochemical, and pathophysiologic features.Neurology (Minneap.) 25 (1975) 16–24
Khan, L. and Bamji, M. S. Plasma carnitine level in children with protein-calorie malnutrition before and after rehabilitation.Clin. Chim. Acta 75 (1977) 163–166
Kølvraa, S., Gregersen, N., Christensen, E. and Hobolth, N.In vitro fibroblast studies in a patient with C6-C10-dicarboxylic aciduria: evidence for a defect in general CoA dehydrogenase.Clin. Chim. Acta 126 (1982) 53–67
Krieger, I., Taqi, Q., Sweeley, C. C. and Snodgrass, P. J. Ornithine transcarbamylase (OTC) deficiency in intermittent Reye’s syndrome due to multiple acyl-CoA dehydrogenase defect.Pediatr. Res. 17 (1983) 292A (Abstr.)
LaBadie, J., Dunn, W. A. and Aronson, N. N. Jr. Hepatic synthesis of carnitine from protein-bound trimethyllysine. Lysosomal digestion of methyllysine-labeled asialo-fetuin.Biochem. J. 160 (1976) 85–95
Liedtke, A. J., Vary, T. C., Nellis, S. H. and Fultz, C. W. Properties of carnitine incorporation in working swine hearts. Effects of coronary flow, ischemia, and excess of fatty acids.Circ. Res. 50 (1982) 767–774
Lindstedt, G. and Lindstedt, S. Cofactor requirements of γ-butyrobetaine hydroxylase from rat liver.J. Biol. Chem. 245 (1970) 4178–4186
Maebashi, M., Kawamura, N., Sato, M., Imamura, A., Yoshinaga, K. and Suzuki, M. Urinary excretion of carnitine in patients with hyperthyroidism and hypothyroidism: augmentation by thyroid hormone.Metabolism 26 (1977a) 351–356
Maebashi, M., Kawamura, N., Sato, M., Imamura, A., Yoshinaga, K. and Suzuki, M. Urinary excretion of carnitine and serum concentrations of carnitine and lipids in patients with hypofunctional endocrine diseases: involvement of adrenocorticoid and thyroid hormones in ACTH-induced augmentation of carnitine and lipids metabolism.Metabolism 26 (1977b) 357–361
Müller-Höcker, J., Pongratz, D., Deufel, T., Trijbels, J. M. F., Endres, W. and Hubner, G. Fatal lipid storage myopathy with deficiency of cytochrome-c-oxidase and carnitine: a contribution to the combined cytochemical-fine structural identification of cytochrome-c-oxidase in long term frozen muscle.Virchows Arch. (Pathol. Anat.) 399 (1983) 11–23
Netzloff, M. L., Kohrman, A. F., Jones, M. Z., Emaus, R. K., Bieber, L. L. and DiMauro, S. Carnitine deficiency associated with renal Fanconi syndrome.J. Neuropathol. Exp. Neurol. 40 (1981) 351 (Abstr.)
Ohtani, Y., Endo, F. and Matsuda, I. Carnitine deficiency and hyperammonemia associated with valproic acid therapy.J. Pediatr. 101 (1982) 782–785
Pande, S. V. and Parvin, R. Characterization of carnitine acylcarnitine translocase system of heart mitochondria.J. Biol. Chem. 251 (1976) 6683–6691
Paturneau-Jouas, M., Amédée-Manesme, O., Bresson, J. L., Masson, M., Bourra, J. M. and Ricour, C. Carnitine levels during long-term total parenteral nutrition (TPN).Abstracts of Free Communications, Fifth International Congress on Neuromuscular Diseases, 1982
Penn, D., Schmidt-Sommerfeld, E. and Pascu, F. Decreased tissue carnitine concentrations in newborn infants receiving total parenteral nutrition.J. Pediatr. 98 (1981) 976–978
Penn, D., Schmidt-Sommerfeld, E. and Wolf, H. Carnitine deficiency in premature infants receiving total parenteral nutrition.Early Hum. Dev. 4 (1980) 23–24
Rebouche, C. J. Carnitine movement across muscle cell membranes. Studies in isolated rat muscle.Biochim. Biophys. Acta 471 (1977) 145–1155
Rebouche, C. J. and Engel, A. G. Tissue distribution of carnitine biosynthetic enzymes in man.Biochim. Biophys. Acta 630 (1980a) 22–29
Rebouche, C. J. and Engel, A. G. Significance of renal γ-butyrobetaine hydroxylase for carnitine biosynthesis in man.J. Biol. Chem. 255 (1980b) 8700–8705
Rebouche, C. J. and Engel, A. G.In vitro analysis of hepatic carnitine biosynthesis in human systemic carnitine deficiency.Clin. Chim. Acta 106 (1980c) 295–300
Rebouche, C. J. and Engel, A. G. Primary systemic carnitine deficiency. I. Carnitine biosynthesis.Neurology (NY) 31 (1981) 813–818
Rebouche, C. J. and Engel, A. G. Carnitine transport in cultured muscle cells and skin fibroblasts from patients with primary systemic carnitine deficiency.In Vitro 18 (1982) 495–500
Rebouche, C. J. and Engel, A. G. Kinetic cempartmental analysis of carnitine metabolism in the dog.Arch. Biochem. Biophys. 220 (1983) 60–70
Rebouche, C. J. and Engel, A. G. Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes: evidence for alterations in tissue carnitine transport.J. Clin. Invest. 73 (1984) 857–867
Rebouche, C. J. and Mack, D. Carnitine transport across rat renal bushbordermembranes (abstract).Fed. Proc. 42 (1983) 1053
Roe, C. R. and Bohan, T. P.l-Carnitine therapy in propionicacidaemia (letter to the editor).Lancet 1 (1982) 1411–1412
Rudman, D., Sewell, C. W. and Ansley, J. D. Deficiency of carnitine in cachectic cirrhotic patients.J. Clin. Invest. 60 (1977) 716–723
Sansaricq, C, Kaufmann, R., DiMauro, S., Schacht, R. G., Greco, A., Goldstein, F., Naylor, E. W., Bazaz, G. and Snyderman, S. E. Mixed form of carnitine deficiency with dicarboxylic-aciduria unresponsive to carnitine.Pediatr. Res. 17 (1983) 295A (Abstr.)
Scarlato, G., Pellegrini, G., Moggio, M., Meola, G. and Frattola, L. Carnitine deficiency and lipid storage myopathy in three patients: analysis of some differential features.Perspect. Inker. Metab. Dis. 3 (1979) 109–128
Scholte, H. R., Meijer, A. E. F. H. and Van Wijngaarden, G.K.et al. Familial carnitine deficiency. A fatal case and subclinical state in a sister.J. Neurol. Sci. 42 (1979) 87–101
Scholte, H. R., Stinis, J. T. and Jennekens, F. G. I. Low carnitine levels in serum of pregnant women (letter to the editor).N. Engl. J. Med. 299 (1978) 1079–1080
Seccombe, D. W., Snyder, F. and Parsons, H. G.l-Carnitine for methylmalonicaciduria (letter to the editor).Lancet 2 (1982) 1401
Shaw, R. D., Shug, A. L. and Olsen, W. A. Studies of carnitine transport by rat small intestine.Pediatr. Res. 17 (1983) 194A
Stanley, C. A., Gonzales, E., Kelley, R. L. and Yang, W. Reduced tissue carnitine associated with a defect in fatty acid beta-oxidation.Diabetes 31, Suppl. 2 (1982) 165A (Abstr.)
Stanley, C. A, Hale, D. E., Whiteman, D. E. H., Coates, P. M., Yudkoff, M., Berry, G. T. and Segal, S. Systemic carnitine (earn) deficiency in isovaleric acidemia (IVA).Pediatr. Res. 17 (1983) 296A (Abstr.)
Tanphaichitr, V. and Broquist, H. P. Role of lysine and e-N-trimethyllysine in carnitine biosynthesis. II. Studies in the rat.J. Biol. Chem. 248 (1973) 2176–2181
Tripp, M. E., Katcher, M. L., Peters, H. A., Gilhert, E. F., Arya, S., Hodach, R. J. and Shug, A. L. Systemic carnitine deficiency presenting as familial endocardial fibroelastosis: a treatable cardiomyopathy.N. Engl. J. Med. 305 (1981) 385–390
Van Hinsbergh, W. V., Veerkamp, J. H., Engelen, P. J. M.et al. Effect ofl-carnitine on the oxidation of leucine and valine by rat skeletal muscle.Biochem. Med. 20 (1978) 115–124
Valkner, K. J. and Bieber, L. L. Short-chain acylcarnitines of human blood and urine.Biochem. Med. 28 (1982) 197–302
Vary, T. C. and Neely, J. R. Sodium dependence of carnitine transport in isolated perfused adult rat hearts.Heart Circ. Physiol. 13 (1983) H247–252
Waber, L. J., Valle, D., Neill, C., DiMauro, S. and Shug, A. Carnitine deficiency presenting as familial cardiomyopathy: a treatable defect in carnitine transport.J. Pediatr. 101 (1982) 700–705
Wolf, G. and Berger, C. R. A. Studies on the biosynthesis and turnover of carnitine.Arch. Biochem. Biophys. 92 (1961) 360–365
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Engel, A.G., Rebouche, C.J. Carnitine metabolism and inborn errors. J. Inher. Metab. Dis. 7 (Suppl 1), 38–43 (1984). https://doi.org/10.1007/BF03047372
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DOI: https://doi.org/10.1007/BF03047372