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Journal of Inherited Metabolic Disease

, Volume 10, Supplement 1, pp 159–198 | Cite as

The inborn errors of mitochondrial fatty acid oxidation

  • C. Vianey-Liaud
  • P. Divry
  • N. Gregersen
  • M. Mathieu
Section V: Diagnostic Methods

Abstract

To date, seven inborn errors of mitochondrial fatty acid oxidation have been identified. A total of about 100 patients in the world have been reported. Clinically the β-oxidation defects are more often characterized by episodic hypoglycaemia leading to a coma mimicking Reye's syndrome. The hypoglycaemia is non-ketotic since the synthesis of ketone bodies is deficient. Periods of decompensation occur when carbohydrate supply is poor, e.g. prolonged fasting, vomiting, or increased caloric requirements, as and when lipid stores are used. Defects in β-oxidation have also been reported to be one cause of sudden infant death syndrome. The diagnosis of these inborn errors is by biochemical investigation since where symptoms suggest such a defect, the precise aetiology cannot be assessed. The biochemical diagnosis is based firstly on identification of abnormal plasma and of urinary metabolites during acute attacks. Derivatives of the ω-oxidation and ω-1-oxidation of medium chain fatty acids have been identified, as well as acylglycine and acylcarnitine conjugates. These metabolites are nearly always absent when patients are in good clinical condition. Secondly, the diagnosis must be based on the identification of the enzymatic defects: this involves global assays which allow a localization of the ‘level’ of the defect (i.e. the oxidation of long, medium or short chain fatty acids) and specific measurement of enzyme activities (acyl-CoA dehydrogenases and electron carriers: ETF and ETF-DH). The diagnosis of these disorders is of prime importance because of the severity of the clinical symptoms. These can be prevented, in some cases, by an appropriate diet (a high carbohydrate, low fat diet, sometimes supplemented withl-carnitine). In other cases, genetic counselling can be offered.

Keywords

Chain Fatty Acid Infant Death Short Chain Fatty Acid Inborn Error Sudden Infant 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Amendt, B. A. and Rhead, W. J. The multiple acyl-coenzyme A dehydrogenation disorders, glutaric aciduria type II and ethylmalonic-adipic aciduria.J. Clin. Invest. 78 (1986) 205–213PubMedGoogle Scholar
  2. Anon. Sudden infant death and inherited metabolic disease (Leader).Lancet 2 (1986) 1073–1075Google Scholar
  3. Bas, S. and Giacobino, J. P. Peroxisomal and mitochondrial palmitoyl coenzyme A β-oxidation activities in rat white adipose tissue and their regulation in hypothyroidism.Arch. Biochem. Biophys. 222 (1983) 416–423PubMedGoogle Scholar
  4. Beckmann, J. D. and Frerman, F. E. Reaction of electron transfer flavoprotein with electron-transfer flavoprotein-ubiquinone oxidoreductase.Biochemistry 24 (1985) 3922–3925PubMedGoogle Scholar
  5. Bennett, M. J., Curnock, D. A., Engel, P. C., Shaw, L., Gray, R. G. F., Hull, D., Patrick, A. D. and Pollitt, R. J. Glutaric aciduria type II: biochemical investigation and treatment of a child diagnosed prenatally.J. Inher. Metab. Dis. 7 (1984) 57–61Google Scholar
  6. Bennett, M. J., Gray, R. G. F., Isherwood, D. M., Murphy, N. and Pollitt, R. J. The diagnosis and biochemical investigation of a patient with a short chain fatty acid oxidation defect.J. Inher. Metab. Dis. 8 Suppl. 2 (1985a) 135–136PubMedGoogle Scholar
  7. Bennett, M. J., Allison, F., Johnston, D. I., Gray, R. G. F., Lowther, G., Fitzsimmons, J. S. and Pollitt, R. J. Prenatal diagnosis of medium chain acyl-CoA dehydrogenase deficiency. SSIEM, 23rd Annual Symposium, Liverpool, 4–6 September (1985b)Google Scholar
  8. Bjorkhem, I. Microsomal dehydrogenation of omega 1 and omega 2 hydroxy fatty acids.Biochim. Biophys. Acta 260 (1972a) 178–184PubMedGoogle Scholar
  9. Bjorkhem, I. On the role of alcohol dehydrogenase in ω-oxidation of fatty acids.Eur. J. Biochem. 30 (1972b) 441–447PubMedGoogle Scholar
  10. Bohm, N., Uy, J., Kiebling, M. and Lehnert, W. Multiple acyl-CoA dehydrogenase deficiency (glutaric aciduria type II), congenital polycystic kidneys, and symmetric warty dysplasia of the cerebral cortex in two newborn brothers. II Morphology and pathogenesis.Eur. J. Pediatr. 139 (1982) 60–65PubMedGoogle Scholar
  11. Bougneres, P. F., Saudubray, J. M. Marsac, C., Bernard, O., Odievre, M. and Girard, J. Fasting hypoglycemia resulting from hepatic carnitine palmitoyl-transferase deficiency.J. Pediatr. 98 (1981) 742–746PubMedGoogle Scholar
  12. Bougneres, P. F., Rocchiccioli, F., Kolvraa, S., Hadchouel, M., Lalau-Keraly, J., Chaussain, J. L., Wadman, S. K. and Gregersen, N. Medium chain acyl CoA dehydrogenase deficiency in two siblings with a Reye-like syndrome.J. Pediatr. 106 (1985) 918–921PubMedGoogle Scholar
  13. Bronfman, M., Inestrosa, N. C., Nervi, F. O. and Leighton, F. Acyl-CoA synthetase and the peroxisomal enzymes of β-oxidation in human liver. Quantitative analysis of their subcellular localization.Biochem. J. 224 (1984), 709–720.PubMedGoogle Scholar
  14. Chalmers, R. A., Tracey, B. M., King, G. S., Pettit, B., Rocchiccioli, F., Saudubray, J. M., Gray, R. G. F., Boue, J., Keeling, J. W. and Lindenbaum, R. H. The prenatal diagnosis of glutaric aciduria type II, using quantitative GC-MS.J. Inher. Metab. Dis. 8 Suppl. 2 (1985), 145–146Google Scholar
  15. Chalmers, R. A., English, N., Hughes, E. A., Noble-Jamieson, C. and Wigglesworth, J. S. Biochemical studies on cultured skin fibroblasts from a baby with long-chain acyl-CoA dehydrogenase deficiency presenting as sudden neonatal death. SSIEM, 24th Annual Symposium, Amersfoort, 9–12 September (1986)Google Scholar
  16. Charpentier, C., Coude, M., Harpey, J. P., Perignon, J. L. and Saudubray, J. M. Screening and quantitative determination of urinary acyl carnitines in disorders of organic acid metabolism. SSIEM, 23rd Annual Symposium, Liverpool, 4–6 September (1985)Google Scholar
  17. Choi, Y. R. and Bieber, L. L. A method for the isolation, identification and quantitation of water-soluble aliphatic acylcarnitines.Anal. Biochem. 79 (1977) 413–418PubMedGoogle Scholar
  18. Christensen, E. Glutaryl-CoA dehydrogenase activity determined with intact electron-transport chain: application to glutaric aciduria type II.J. Inher. Metab. Dis. 7 (1984) 103–104PubMedGoogle Scholar
  19. Christensen, E., Kolvraa, S. and Gregersen, N. Glutaric aciduria type II: evidence for a defect related to the electron transfer flavoprotein or its dehydrogenase.Pediatr. Res. 18 (1984) 663–667PubMedGoogle Scholar
  20. Coates, P. M., Hale, D. E., Katz, M. R., Stanley, C. A. and Hall, C. L. Detection of medium chain acyl-CoA dehydrogenase deficiency in leukocytes.Pediatr. Res. 17 (1983), 288 A.Google Scholar
  21. Coates, P. M., Hale, D. E., Stanley, C. A., Corkey, B. E. and Cortner, J. A. Genetic deficiency of medium-chain acyl CoA dehydrogenase: studies in cultured skin fibroblasts and peripheral mononuclear leukocytes.Pediatr. Res. 19 (1985), 671–676PubMedGoogle Scholar
  22. Coates, P. M., Hale, D. E., Stanley, C. A., Kelley, R. I. and Corkey, B. E. Diagnosis of acyl-CoA dehydrogenase deficiencies. SSIEM, 24th Annual Symposium, Amersfoort, 9–12 September (1986a)Google Scholar
  23. Coates, P. M., Hale, D. E. and Winter, S. C. Short-chain acyl CoA dehydrogenase deficiency associated with severe skeletal muscle weakness and muscle carnitine deficiency.Pediatr. Res. 20 (1986b) 328AGoogle Scholar
  24. Colle, E., Mamer, O. A., Montgomery, J. A. and Miller, J. D. Episodic hypoglycemia with hydroxy fatty acid excretion.Pediatr. Res. 17 (1983) 171–176PubMedGoogle Scholar
  25. Coude, F. X., Ogier, H., Charpentier, C., Thomassin, G., Checoury, A., Amedee-Manesme, O., Saudubray, J. M. and Frezal, J. Neonatal glutaric aciduria type II: an X-linked recessive inherited disorder.Hum. Genet. 59 (1981), 263–265PubMedGoogle Scholar
  26. Del Valle, J. A., Garcia, M. J., Merinero, B., Perez-Cerda, C., Roman, F., Jimenez, A., Ugarte, M., Martinez-Pardo, M., Ludena, C., Camarero, C., Del Olmo, R., Duran, M. and Wadman, S. K. A new patient with dicarboxylic aciduria suggestive of medium-chain acyl-CoA dehydrogenase deficiency presenting as Reye's syndrome.J. Inher. Metab. Dis. 7 (1984), 62–64Google Scholar
  27. Di Donato, S., Peluchetti, D., Rimoldi, M., Mora, M. and Garavaglia, B. Systemic carnitine deficiency: clinical, biochemical and morphological cure withl-carnitine.Neurology 34 (1984) 157–162PubMedGoogle Scholar
  28. Divry, P., David, M., Gregersen, N., Kolvraa, S., Christensen, E., Collet, J. P., Dellamonica, C. and Cotte, J. Dicarboxylic aciduria due to medium chain acyl-CoA dehydrogenase defect. A cause of hypoglycemia in childhood.Acta Paediatr. Scand. 72 (1983) 943–949PubMedGoogle Scholar
  29. Divry, P., Vianey-Liaud, C. and Cotte, J. Gas chromatography-mass spectrometry (GC-MS) diagnosis of two cases of medium chain acyl CoA dehydrogenase deficiency.J. Inher. Metab. Dis. 7 Suppl. 1 (1984) 44–47PubMedGoogle Scholar
  30. Duran, M., de Klerk, J. B. C., Van Pelt, J., Wadman, S. K., Scholte, H. R., Beekman, R. P. and Jennekens, F. G. I. The analysis of plasma and urinary organic acids during prolonged fasting differentiates between systemic carnitine deficiency and a defect of fatty acid oxidation.J. Inher. Metab. Dis. 6 Suppl. 2 (1983a) 121–122PubMedGoogle Scholar
  31. Duran, M., Walther, F. J., Bruinvis, L. and Wadman, S. K. The urinary excretion of ethylmalonic acid: what level requires further attention?Biochem. Med. 29 (1983b) 171–175PubMedGoogle Scholar
  32. Duran, M., de Klerck, J. B. C., Wadman, S. K., Bruinvis, L. and Ketting, D. The differential diagnosis of dicarboxylic aciduria.J. Inher. Metab. Dis. 7 Suppl. 1 (1984) 48–51PubMedGoogle Scholar
  33. Duran, M., Ketting, D., Dorland, L. and Wadman, S. K. The identification of acylcarnitines by desorption chemical ionization mass spectrometry.J. Inher. Metab. Dis. 8 Suppl. 2 (1985a) 143–144Google Scholar
  34. Duran, M., Ketting, D., van Vossen, R., Beckeringh, T. E., Dorland, L., Bruinvis, L. and Wadman, S. K. Octanoyl glucuronide excretion in patients with a defective oxidation of medium-chain fatty acids.Clin. Chim. Acta 152 (1985b) 253–260PubMedGoogle Scholar
  35. Duran, M., Mitchell, G., de Klerck, J. B. C., de Jagar, J. P., Hofkamp, M., Bruinvis, L., Ketting, D., Saudubray, J. M. and Wadman, S. K. Octanoic acidemia and octanoylcarnitine excretion with dicarboxylic aciduria due to defective oxidation of medium-chain fatty acids.J. Pediatr. 107 (1985c) 397–404PubMedGoogle Scholar
  36. Dusheiko, G., Kew, M. C., Joffe, B. I., Lewin, J. R., Path, F. F., Mantagos, S. and Tanaka, K. Recurrent hypoglycemia associated with glutaric aciduria type II in adults.N. Engl. J. Med. 301 (1979) 1405–1409PubMedGoogle Scholar
  37. de Duve, C., Beaufay, H., Jacques, P., Rahamly, Y., Sellinger, O. Z., Wattiaux, R. and de Conninck, S. Intracellular distribution of catalase and of some oxidases in rat liver.Biochim. Biophys. Acta 40 (1960) 186–187PubMedGoogle Scholar
  38. Engel, A. G. and Rebouche, C. J. Carnitine metabolism and inborn errors.J. Inher. Metab. Dis. 7 (1984) 38–43Google Scholar
  39. Frerman, F. E. and Goodman, S. I. Fluorimetric assay of acyl-CoA dehydrogenase in normal and mutant human fibroblasts.Biochem. Med. 33 (1985a) 38–44PubMedGoogle Scholar
  40. Frerman, F. E. and Goodman, S. I. Deficiency of electron transfer flavoprotein or electron transfer flavoprotein: ubiquinone oxidoreductase in glutaric acidemia type II fibroblasts.Proc. Natl. Acad. Sci. USA 82 (1985b) 4517–4520PubMedGoogle Scholar
  41. Furuta, S., Miyazawa, S. and Hashimoto, T. Purification and properties of rat liver acyl-CoA dehydrogenases and electron transfer flavoprotein.J. Biochem. 90 (1981) 1739–1750PubMedGoogle Scholar
  42. Gohil, K., Jones, D. A. and Edwards, R. H. T. Fatty acid oxidation in mitochondria from needle biopsy samples of human skeletal muscle.Clin. Sci. 66 (1984) 173–178PubMedGoogle Scholar
  43. Goodman, S. I. and Frerman, F. E. Glutaric aciduria type II (multiple acyl-CoA dehydrogenation deficiency) acidemia.J. Inher. Metab. Dis. 7 (1984) 33–37PubMedGoogle Scholar
  44. Goodman, S. I., McCabe, E. R., Fennessey, P. V. and Mace, J. W. Multiple acyl-CoA dehydrogenase deficiency (glutaric aciduria type II) with transient hypersarcosinemia and sarcosinuria; possible inherited deficiency of an electron transfer flavoprotein.Pediatr. Res. 14 (1980) 12–17PubMedGoogle Scholar
  45. Goodman, S. I., Stene, D. O., McCabe, E. R. B., Noremberg, M. D., Shikes, R. H., Stumpf, D. A. and Blackburn, G. K. Glutaric aciduria type II: clinical, biochemical and morphological considerations.J. Pediatr. 100 (1982) 946–950PubMedGoogle Scholar
  46. Goodman, S. I., Reale, M. and Berlow, S. Glutaric acidemia type II: a form with deleterious intrauterine effects.J. Pediatr. 102 (1983) 411–413PubMedGoogle Scholar
  47. Green, A., Marshall, T. G., Bennett, M. J., Gray, R. G. F. and Pollitt, R. J. Riboflavin-responsive ethylmalonic-adipic aciduria.J. Inher. Metab. Dis. 8 (1985) 67–70PubMedGoogle Scholar
  48. Gregersen, N. Fatty acyl-CoA dehydrogenase deficiency: enzyme measurement and studies on alternative metabolism.J. Inher. Metab. Dis. 7 Suppl. 1 (1984) 28–32PubMedGoogle Scholar
  49. Gregersen, N. Riboflavin-responsive defects of beta oxidation.J. Inher. Metab. Dis. 8 Suppl. 1 (1985) 65–69PubMedGoogle Scholar
  50. Gregersen, N., Lauritzen, R. and Rasmussen, K. Suberylglycine excretion in the urine from a patient with dicarboxylic aciduria.Clin. Chim. Acta 70 (1976) 417–425PubMedGoogle Scholar
  51. Gregersen, N., Kolvraa, S., Rasmussen, K., Christensen, E., Brandt, N. J., Ebbessen, F. and Hansen, F. H. Biochemical studies in a patient with defects in the metabolism of acyl-CoA and sarcosine: another possible case of glutaric aciduria type II.J. Inher. Metab. Dis. 3 (1980a) 67–72PubMedGoogle Scholar
  52. Gregersen, N., Rosleff, F., Kolvraa, S., Hobloth, N., Rasmussen, K. and Lauritzen, R. Non-ketotic C6–C10 dicarboxylic aciduria: biochemical investigations of two cases.Clin. Chim. Acta 102 (1980b) 179–189PubMedGoogle Scholar
  53. Gregersen, N., Wintzensen, H., Kolvraa, S., Christensen, E., Christensen, M. F., Brandt, N. J. and Rasmussen, K. C6–C10 dicarboxylic aciduria: investigation of a patient with riboflavin responsive multiple acyl-CoA dehydrogenation defect.Pediatr. Res. 16 (1982) 861–868PubMedGoogle Scholar
  54. Gregersen, N., Kolvraa, S., Rasmussen, K., Mortensen, P. B., Divry, P., David, M. and Hobolth, N. General (medium chain) acyl-CoA dehydrogenase deficiency (non ketotic dicarboxylic aciduria): quantitative urinary excretion pattern of 23 biologically significant organic acids in 3 cases.Clin. Chim. Acta 132 (1983a) 181–191PubMedGoogle Scholar
  55. Gregersen, N., Kolvraa, S. and Mortensen, P. B. On the origin of C6–C10 dicarboxylic and C6–C10ω-1 hydroxymonocarboxylic acids in human and rat with acyl-CoA deficiencies:in vitro studies on theω- andω-1 oxidation of medium-chain (C6–C12) fatty acids in human and rat liver.Pediatr. Res. 17 (1983b) 828–834PubMedGoogle Scholar
  56. Gregersen, N., Kolvraa, S. and Mortensen, P. B. Acyl-CoA: glycineN-acyltransferase:in vitro studies on the conjugation of straight and branched acyl-CoA esters in human liver.Biochem. Med. Metab. Biol. 35 (1986) 210–218PubMedGoogle Scholar
  57. Hale, D. E., Coates, P. M., Stanley, C. A., Lortner, J. A. and Hall, C. L. Long-chain acyl-CoA dehydrogenase deficiency.Pediatr. Res. 17 (1983) 290AGoogle Scholar
  58. Hale, D. E., Batshaw, M. L., Coates, P. M., Frerman, F. E., Goodman, S. I., Singh, I. and Stanley, C. A. Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of non-ketotic hypoglycemia.Pediatr. Res. 19 (1985) 666–671PubMedGoogle Scholar
  59. Hall, C. L. and Kamin, H. The purification and some properties of electron transfer flavoprotein and general fatty acid coenzyme A dehydrogenase from pig liver mitochondria.J. Biol. Chem. 250 (1975) 3476–3486PubMedGoogle Scholar
  60. Harpey, J. P., Charpentier, C., Goodman, S. I., Darbois, Y., Lefebvre, G. and Sebbah, J. Multiple acyl-CoA dehydrogenase deficiency occurring in pregnancy and caused by a defect in riboflavin metabolism in the mother.J. Pediatr. 103 (1983a) 394–398PubMedGoogle Scholar
  61. Harpey, J. P., Charpentier, C. and Goodman, S. I. Multiple acyl-CoA dehydrogenase deficiency responsive to riboflavin, a family study. SSIEM, 21st Annual Symposium, Lyon, 6–9 September (1983b)Google Scholar
  62. Harpey, J. P., Charpentier, C. and Ceballos, I. C6–C10 dicarboxylic aciduria responsive to riboflavin. SSIEM, 22nd Annual Symposium, Newcastle 4–7 September (1984)Google Scholar
  63. Harpey, J. P., Charpentier, C. and Coude, M. Methylene-blue for riboflavin-unresponsive glutaric aciduria type II.Lancet 15 (1986) 391Google Scholar
  64. Howat, A. J., Bennett, M. J. and Variend, S. Deficiency of medium chain fatty acylcoenzyme-A dehydrogenase presenting as the sudden infant death syndrome.Br. Med. J. 288 (1984) 976Google Scholar
  65. Howat, A. J., Bennett, M. J., Variend, S., Shaw, L. and Engel, P. C. Defect of metabolism of fatty acids in the sudden infant death syndrome.Br. Med. J. 290 (1985) 1771–1773Google Scholar
  66. Husain, M. and Steenkamp, D. J. Electron transfer flavoprotein from pig liver mitochondria: a simple purification and re-evaluation of some of the molecular properties.Biochem. J. 209 (1983) 541–545PubMedGoogle Scholar
  67. Ikeda, Y. and Tanaka, K. Purification and characterization of isovaleryl-coenzyme A dehydrogenase from rat liver mitochondria.J. Biol. Chem. 258 (1983) 1077–1085PubMedGoogle Scholar
  68. Ikeda, Y., Dabrowski, C. and Tanaka, K. Separation and properties of five distinct acyl-CoA dehydrogenases from rat liver mitochondria. Identification of a new 2-methyl branched chain acyl-CoA dehydrogenase.J. Biol. Chem. 258 (1983) 1066–1076PubMedGoogle Scholar
  69. Ikeda, Y., Hale, D. E., Kesse, S. M., Coates, P. M. and Tanaka, K. Biosynthesis of variant medium chain acyl-CoA dehydrogenase in cultured fibroblasts from patients with medium chain acyl-CoA dehydrogenase deficiency.Pediatr. Res. 20 (1986) 843–847PubMedGoogle Scholar
  70. Jakobs, C., Sweetman, L., Wadman, S. K., Duran, M., Saudubray, J. M. and Nyhan, W. L. Prenatal diagnosis of glutaric aciduria type II by direct chemical analysis of dicarboxylic acids in amniotic fluid.Eur. J. Pediatr. 141 (1984) 153–157PubMedGoogle Scholar
  71. Karpati, G., Carpentier, S., Engel, A., Watters, G., Alan, J., Rothman, S., Klassen, G. and Mamer, O. A. The syndrome of systemic carnitine deficiency. Clinical, morphological, biochemical and pathophysiologic features.Neurology 25 (1975) 16–24PubMedGoogle Scholar
  72. McKean, M. C., Beckmann, J. D. and Frerman, F. E. Subunit structure of electron transfer flavoprotein.J. Biol. Chem. 258 (1983) 1866–1870PubMedGoogle Scholar
  73. Kolvraa, S. and Gregersen, N. Methods for measurement of fatty acid β-oxidation and acyl-CoA dehydrogenase activity in cultured fibroblasts.J. Inher. Metab. Dis. 5 Suppl. 1 (1982) 31–32Google Scholar
  74. Kolvraa, S. and Gregersen, N.In vitro studies on the oxidation of medium-chain dicarboxylic acids in rat liver.Biochim. Biophys. Acta 876 (1986) 515–525PubMedGoogle Scholar
  75. Kolvraa, 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 acyl-CoA dehydrogenase.Clin. Chim. Acta 126 (1982) 53–67PubMedGoogle Scholar
  76. Kondrup, J. and Lazarow, P. B. Flux of palmitate through the peroxisomal and mitochondrial β-oxidation systems in isolated rat hepatocytes.Biochim. Biophys. Acta 835 (1985) 147–153PubMedGoogle Scholar
  77. Lazarow, B. P. Rat liver peroxisomes catalyse the β-oxidation of fatty acids.J. Biol. Chem. 253 (1978) 1522–1528PubMedGoogle Scholar
  78. Lazarow, B. P. and de Duve, C. A fatty acyl-CoA oxidizing system in rat liver peroxisomes: enhancement by clofibrate, a hypolipidemic drug.Proc. Natl. Acad. Sci. USA 73 (1976) 2043–2046PubMedGoogle Scholar
  79. Lazarow, B. P., Fujiki, Y., Mortensen, R. and Hashimoto, T. Identification of β-oxidation enzymes among peroxisomal polypeptides. Increase in Coomassie blue-stainable protein after clofibrate treatment.FEBS Lett 150 (1982) 307–310PubMedGoogle Scholar
  80. Lehnert, W., Wendel, U., Lindenmaier, S. and Bohm, N. Multiple acyl-CoA dehydrogenation deficiency (glutaric aciduria type II). Congenital polycystic kidneys, and symmetric warty dysplasia of the cerebral cortex in two brothers. I. Clinical, metabolical and biochemical findings.Eur. J. Pediatr. 139 (1982) 56–59PubMedGoogle Scholar
  81. Lu, A. Y. H. and Coon, M. J. Role of hemoprotein P450 in fatty acidω-hydroxylation in a soluble enzyme system from liver microsomes.J. Biol. Chem. 243 (1968) 1331–1332PubMedGoogle Scholar
  82. Mamer, O. A., Montgomery, J. A. and Coole, E. Profiles in altered metabolism. III. (ω-1)-hydroxyacid excretion in a case of episodic hypoglycemia.Biomed. Mass Spectr. 7 (1980) 53–57Google Scholar
  83. Mantagos, S., Genel, M. and Tanaka, K. Ethylmalonic adipic aciduria.In vivo andin vitro studies indicating deficiency of activities of multiple acyl-CoA dehydrogenases.J. Clin. Invest. 64 (1979) 1580–1589PubMedGoogle Scholar
  84. Mitchell, G., Saudubray, J. M., Benoit, Y., Labarthe, J. C., Ogier, H., Divry, P. and Frezal, J. Fatty acid β-oxidation defects: diagnosis in fibroblast culture. SSIEM, 21st Annual Symposium, Lyon, 6–9 September (1983a)Google Scholar
  85. Mitchell, G., Saudubray, J. M., Benoit, Y., Rocchiccioli, F., Charpentier, C., Ogier, H. and Boue, J. Antenatal diagnosis of glutaric aciduria type II.Lancet 1 (1983b) 1099Google Scholar
  86. Moon, A. and Rhead, W. J. Complementation analysis of fatty acid oxidation disorders.J. Clin. Invest. (in press)Google Scholar
  87. Mooy, P. D., Giesberts, M. A. H., van Gelderen, H. H., Scholte, H. R., Luyt-Houwen, I. E. M., Przyrembel, H. and Blom, W. Glutaric aciduria type II: multiple defects in isolated muscle mitochondria and deficient β-oxidation in fibroblasts.J. Inher. Metab. Dis. 7 (1984) 101–102PubMedGoogle Scholar
  88. Mortensen, P. B. The possible antiketogenic and gluconeogenic effect of theω-oxidation of fatty acids in rats.Biochim. Biophys. Acta 620 (1980) 177–185PubMedGoogle Scholar
  89. Mortensen, P. B. Urinary excretion of C4–C10 dicarboxylic acids and antiketogenic properties of adipic acid in ketogenic stimulated rats due to diabetes, long chain and short chain monocarboxylic acids.Biochim. Biophys. Acta 664 (1981a) 335–348PubMedGoogle Scholar
  90. Mortensen, P. B. C6–C10 dicarboxylic aciduria in starved, fat fed and diabetic rats receiving decanoic acid or medium chain triacylglycerol. Anin vivo measure of the rate of β-oxidation of fatty acids.Biochim. Biophys. Acta 664 (1981b) 349–355PubMedGoogle Scholar
  91. Mortensen, P. B. and Gregersen, N. Medium-chain triglyceride medication as a pitfall in the diagnosis of non-ketotic C6–C10 dicarboxylic acidurias.Clin. Chim. Acta 103 (1980) 33–37PubMedGoogle Scholar
  92. Mortensen, P. B. and Gregersen, N. The biological origin of ketotic dicarboxylic aciduria.In vivo andin vitro investigations of theω-oxidation of C6–C16 monocarboxylic acids in unstarved, starved and diabetic rats.Biochim. Biophys. Acta 666 (1981) 394–404PubMedGoogle Scholar
  93. Mortensen, P. B., Kolvraa, S., Gregersen, N. and Rasmussen, K. Cyanide insensitive and clofibrate enhanced β-oxidation of dodecanedioic acid in rat liver. An indication of peroxisomal β-oxidation ofN-dicarboxylic acids.Biochim. Biophys. Acta 713 (1982) 393–397PubMedGoogle Scholar
  94. Mortensen, P. B., Gregersen, N., Rasmussen, K. and Kolvraa, S. The β-oxidation of dicarboxylic acids in isolated mitochondria and peroxisomes.J. Inher. Metab. Dis. 6 (1983) 123–124PubMedGoogle Scholar
  95. Naylor, E. W., Mosovich, L. L. Guthrie, R., Evans, J. E. and Tieckelmann, H. Intermittent non-ketotic dicarboxylic aciduria in two siblings with hypoglycaemia: an apparent defect in β-oxidation of fatty acids.J. Inher. Metab. Dis. 3 (1980) 19–24PubMedGoogle Scholar
  96. Niederwieser, A., Steinmann, B., Exner, U., Neuheiser, F., Redwik, U., Wang, M., Rampini, S. and Wendel, U. Multiple acyl-CoA dehydrogenation deficiency (MADD) in a boy with non-ketotic hypoglycemia, hepatomegaly, muscle hypotonia and cardiomyopathy: detection ofN-isovalerylglutamic acid and its monoamide.Helvet. Paediatr. Acta 38 (1983) 9–26Google Scholar
  97. Norseth, J. and Thomassen, M. S. Stimulation of microperoxisomal β-oxidation in rat heart by high fat diets.Biochim. Biophys. Acta 751 (1983) 312–320PubMedGoogle Scholar
  98. Osmundsen, H. and Bremer, J. A spectrophotometric procedure for rapid and sensitive measurements of β-oxidation.Biochem. J. 164 (1977) 621–633PubMedGoogle Scholar
  99. Pettersen, J. E.In vivo studies on the metabolism of hexanedioic acid.Clin. Chim. Acta 58 (1975) 43–50PubMedGoogle Scholar
  100. Preiss, B. and Bloch, K.ω-Oxidation of long chain fatty acids in rat liver.J. Biol. Chem. 239 (1964) 85–88PubMedGoogle Scholar
  101. Przyrembel, M., Wendel, U., Becker, K., Bremer, H., Bruinvis, L., Ketting, D. and Wadman, S. K. Glutaric aciduria type II: report on a previously underscribed metabolic disorder.Clin. Chim. Acta 66, (1976) 227–239PubMedGoogle Scholar
  102. Rhead, W. and Amendt, B. A. Electron-transferring flavoprotein deficiency in the multiple acyl-CoA dehydrogenation disorders. Glutaric aciduria type II and ethylmalonic-adipic aciduria.J. Inher. Metab. Dis. 7 (1984) 99–100PubMedGoogle Scholar
  103. Rhead, W. and Fritchman, K. N. Riboflavin-responsive ethylmalonic-adipic aciduria (RR-EMA)in vitro confirmation of vitamin responsiveness in intact fibroblasts.Pediatr. Res. 17 (1983) 218AGoogle Scholar
  104. Rhead, W. J. and Roettger, V. Defective mitochondrial FAD uptake in riboflavin responsive (RR) multiple acyl-CoA dehydrogenation deficiency (MAD). SSIEM, 24th Annual Symposium, Amersfoort, 9–12 September (1986)Google Scholar
  105. Rhead, W. and Tanaka, K. Demonstration of a specific mitochondrial isovaleryl-CoA dehydrogenase deficiency in fibroblasts from patients with isovaleric acidemia.Proc. Natl. Acad. Sci. USA 77 (1980) 580–583PubMedGoogle Scholar
  106. Rhead, W., Mantagos, S. and Tanaka, K. Glutaric aciduria type II:in vitro studies on substrate oxidation, acyl-CoA dehydrogenases, and electron transferring flavoprotein in cultured skin fibroblasts.Pediatr. Res. 14 (1980) 1339–1342PubMedGoogle Scholar
  107. Rhead, W., Hall, C. L. and Tanaka, K. Novel tritium release assays for isovaleryl-CoA and butyryl-CoA dehydrogenases.J. Biol. Chem. 256 (1981) 1616–1624PubMedGoogle Scholar
  108. Rhead, W., Amendt, B. A., Fritchman, K. S. and Felts, S. J. Dicarboxylic aciduria: deficient [1-14C]octanoate oxidation and medium chain acyl-CoA dehydrogenase in fibroblasts.Science 221 (1983a) 73–75PubMedGoogle Scholar
  109. Rhead, W., Fritchman, K. S., Moon, A. and Grundmeyer, P. A. On the inheritance of glutaric aciduria type II (GA-II). SSIEM, 21st Annual Symposium, Lyon, 6–9 September (1983b)Google Scholar
  110. Rhead, W., Fritchman, K. N. and Grundmeyer, P. A. Evidence supporting autosomal recessive inheritance of glutaric aciduria type II (GA-II).Pediatr. Res. 17 (1983c) 218AGoogle Scholar
  111. Robins, K. C. Enzymaticω-oxidation of fatty acids.Fed. Proc. 20 (1964) 272–279Google Scholar
  112. Roe, C. R., Millington, D. S., Maltby, D. A., Bohan, T. P., Kahler, S. G. and Chalmers, R. A. Diagnostic and therapeutic implications of medium-chain acyl carnitines in the medium-chain acyl-CoA dehydrogenase deficiency.Pediatr. Res. 19 (1985) 459–466PubMedGoogle Scholar
  113. Roe, C. R., Millington, D. S., Maltby, D. A. and Kinneprew, P. Recognition of medium-chain acyl-CoA dehydrogenase deficiency in asymptomatic siblings of children dying of sudden infant death or Reye-like syndromes.J. Pediatr. 108 (1986) 13–18PubMedGoogle Scholar
  114. Ruzicka, F. J. and Beinert, H. A. A new iron-sulfur flavoprotein of the respiratory chain: a component of fatty acid β-oxidation pathway.J. Biol. Chem. 252 (1977) 8440–8445PubMedGoogle Scholar
  115. Sakurai, T., Miyakawa, S., Furuta, S. and Hashimoto, T. Riboflavin deficiency and β-oxidation systems in rat liver.Lipids 17 (1982) 598–605PubMedGoogle Scholar
  116. Saudubray, J. M., Marsac, C., Limal, J. M., Dumurgier, E., Charpentier, C., Ogier, H. and Coude, F. X. Variation in plasma ketone bodies during a 24 hour fast in normal and hypoglycemic children: relationship to age.J. Pediatr. 98 (1981) 904–908PubMedGoogle Scholar
  117. Saudubray, J. M., Coude, F. X., Demaugre, F., Johnson, C., Gibson, K. M. and Nyhan, W. L. Oxidation of fatty acids in cultured fibroblasts. A model system for the detection and study of defects in oxidation.Pediatr. Res. 16 (1982) 877–881PubMedGoogle Scholar
  118. Schutgens, R. B. H., Scholte, H. R., Luyt-Houwen, I. E. M., Veder, H. A., Devisser, M. and Bethlem, J. Glutaric aciduria type II; clinical and biochemical observations and riboflavin treatment in four sisters. SSIEM, 21st Annual Symposium, Lyon, 6–9 September (1983)Google Scholar
  119. Shigematsu, Y., Momoi, T., Sudo, M. and Suzuki, Y. (ω-1)-Hydroxymonocarboxylic acids in urine of infants fed medium-chain triglycerides.Clin. Chem. 27 (1981) 1661–1664PubMedGoogle Scholar
  120. Staeffen, J., Rabinowitz, J. L., Aumonier, P., Ballen, P., Ferrer, J., Terme, R., Series, C. and Meyerson, R. M. Hyperoctanoatemia and the hepatic encephalopathy of cirrhosis.Nouv. Press. Med. 8 (1979) 1663–1666Google Scholar
  121. Stanley, C. A., Gonzales, E., Yang, W., Kelley, R. I., and Baker, L. Hypoketotic hypoglycemia. Evidence for a new defect in fatty acid oxidation.Pediatr. Res. 16 (1982) 264AGoogle Scholar
  122. Stanley, C. A., Hale, D. E., Coates, P. M., Hall, C. L., Corkey, B. E., Yang, N., Kelley, R. I., Gonzales, E. L., Williamson, J. R. and Baker, L. Medium-chain acyl-CoA dehydrogenase deficiency in children with non-ketotic hypoglycemia and low carnitine levels.Pediatr. Res. 17 (1983) 877–884PubMedGoogle Scholar
  123. Steinmann, B., Neiderwieser, A., Kuster, T., Bugher, H. U., Huch, A. and Wendel, U. Prenatal diagnosis of multiple acyl-CoA dehydrogenation deficiency (MADD). SSIEM, 21st Annual Symposium, Lyon, 6–9 September (1983)Google Scholar
  124. Sweetman, L., Nyhan, W. L., Trauner, D. A., Merritt, T. A. and Singh, M. Glutaric aciduria type II.J. Pediatr. 96 (1980) 1020–1026PubMedGoogle Scholar
  125. Thomassen, M. S., Christiansen, E. N. and Norum, K. R. characterization of the stimulatory effect of high-fat diets on peroxisomal β-oxidation in rat liver.Biochem. J. 206 (1982) 195–202PubMedGoogle Scholar
  126. Tracey, B. M., Chalmers, R. A., Rosankiewicz, J. R., de Sousa, C. and Stacey, T. E. Acylcarnitines in urine in medium-chain acyl-CoA dehydrogenase deficiency measured by quantitative high pressure liquid chromatography.Biochem. Soc. Trans. 14 (1986) 700–701Google Scholar
  127. Trauner, D. Regional cerebral Na+-K+ ATPase activity following octanoate administration.Pediatr. Res. 16 (1982) 877–881PubMedGoogle Scholar
  128. Truscott, R. J. W., Hick, L., Pullin, C., Halpern, B., Wilcken, B., Griffiths, H., Silink, M., Kilham, H. and Grunseit, F. Dicarboxylic aciduria: the response to fasting.Clin. Chim. Acta 94 (1979) 31–39PubMedGoogle Scholar
  129. Turnbull, D. M., Sherratt, H. S. A., Davies, D. M. and Sykes, A. G. Tetracyano-2,2-bipyridineiron (III), an improved electron acceptor for the spectrophotometric assay of β-oxidation and of succinate dehydrogenase in intact mitochondria.Biochem. J. 206 (1982) 511–516PubMedGoogle Scholar
  130. Turnbull, D. M., Bartlett, K., Stevens, D. L., Alberti, K. G., Gibson, G. J., Johnson, M. A., McCulloch, A. J. and Sherratt, H. S. A. Short-chain acyl-CoA dehydrogenase deficiency associated with a lipid-storage myopathy and secondary carnitine deficiency.N. Engl. J. Med. 311 (1984) 1232–1236PubMedGoogle Scholar
  131. Verkade, P. E. and van der Lee, J. Research on fat metabolism.Biochem. J. 28 (1934) 31–40Google Scholar
  132. Vianey-Liaud, C., Dumoulin, R., Divry, P., Teyssier, G., Guibaud, P., Rousson, R. and Zabot, M. T. Long chain acyl-CoA dehydrogenase deficiency and systemic carnitine deficiency: differential diagnosis in fibroblast culture byL-carnitine addition. SSIEM, 24th Annual Symposium, Amersfoort, 9–12 September (1986)Google Scholar
  133. Wada, F., Shibata, H., Goto, M. and Sakamoto, Y. Participation of the microsomal electron transport system involving cytochrome P450 inω-oxidation of fatty acids.Biochim. Biophys. Acta 162 (1968) 518–524PubMedGoogle Scholar
  134. Wada, F. and Usami, M. Studies of fatty acidω-oxidation. Antiketogenic effect and gluconeogenicity of dicarboxylic acids.Biochim. Biophys. Acta 487 (1977) 261–268Google Scholar
  135. Wakabayashi, K. and Shimazono, N. Studies on theω-oxidation of fatty acidsin vitro. I. Overall reaction and intermediate.Biochim. Biophys. Acta 70 (1963) 132–142PubMedGoogle Scholar
  136. Yang, W., Roth, K. S. and Coates, P. M. Hypoglycemic, hypoketotic dicarboxylic aciduria. A possible defect in fatty acid (FA) oxidation.Pediatr. Res. 16 (1982) 267AGoogle Scholar

Copyright information

© SSIEM and MTP Press Limited 1987

Authors and Affiliations

  • C. Vianey-Liaud
    • 1
  • P. Divry
    • 1
  • N. Gregersen
    • 2
  • M. Mathieu
    • 1
  1. 1.Laboratoire de BiochimieHôpital DebrousseLyon Cedex 05France
  2. 2.University Department for Clinical ChemistryAarhus KommunehospitalAarhus CDenmark

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