Disorders of Fatty Acid Oxidation

  • C. A. Stanley

Summary

The disorders of fatty acid oxidation comprise ten defects in the steps of mitochondrial oxidation of long-chain fatty acids (Table 1). These disorders are rather recent additions to the list of inherited metabolic diseases. The first was reported in 1973 [20] and most have only been described since 1980. Additional defects in the other nine enzyme steps in this pathway are likely to be defined in the near future. Most of the disorders that have been identified present with recurrent episodes of fasting coma and hypoglycemia. In a few, the clinical manifestations include chronic muscle weakness and cardiomyopathy. Although these disorders of fatty acid oxidation are associated with a high risk of mortality during acute episodes, once diagnosed, simple avoidance of prolonged fasts is usually sufficient treatment and the long-term prognosis is most often excellent.

Keywords

Ketone Cardiomyopathy NADH Leucine Triglyceride 

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References

Reviews

  1. 1.
    Stanley CA (1987) New genetic defects in mitochondrial fatty acid oxidation and carnitine deficiency. Adv Pediatr 34: 59–88PubMedGoogle Scholar
  2. 2.
    Tanaka K, Coates PM (eds) (1989) Clinical, biochemical, and molecular aspects of fatty acid oxidation. Liss, New YorkGoogle Scholar
  3. 3.
    Roe CR, Coates PM (1989) Acyl-CoA dehydrogenase deficiencies. In: Scriver CR, et al. (eds) The metabolic basis of inherited disease, 6th edn. McGraw-Hill, New York pp 889–914Google Scholar

MCAD Deficiency

  1. 4.
    Stanley CA, Hale DE, Coates PM, et al. (1983) Medium-chain acyl-CoA dehydrogenase deficiency in children with non-ketotic hypoglycemia and low carnitine levels. Pediatr Res 17: 877–884PubMedCrossRefGoogle Scholar
  2. 5.
    Coates PM, Hale DE, Stanley CA, et al. (1985) Genetic deficiency of medium-chain acyl coenzyme A dehydrogenase: studies in cultured skin fibroblasts and peripheral mononuclear leukocytes. Pediatr Res 19: 672–676CrossRefGoogle Scholar
  3. 6.
    Roe CR, Millington DAM, Bohan TP, et al. (1985) Diagnostic and therapeutic implications of medium-chain acylcarnitines in the medium-chain acyl-CoA dehydrogenase deficiency. Pediatr Res 19: 459–466PubMedCrossRefGoogle Scholar
  4. 7.
    Kolvraa S, Gregersen N, Christensen E, et al. (1982) 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: 53–67PubMedCrossRefGoogle Scholar
  5. 8.
    Rinaldo P, O’Shea JJ, Coates PM, et al. (1988) Medium chain acyl-CoA dehydrogenase deficiency: diagnosis by stable isotope dilution analysis of urinary n-hexanoyl glycine and 3-phenyl propionylglycine. N Engl J Med 319: 1308–1313PubMedCrossRefGoogle Scholar
  6. 9.
    Duran M, Bruinvis L, Ketting D, DeKlerk JB, Wadman SK (1988) cis-4-Decenoic acid in plasma: a characteristic metabolite in medium-chain acyl-CoA dehydrogenase deficiency. Clin Chem 34: 548–551Google Scholar

LCAD Deficiency

  1. 10.
    Hale DE, Batshaw ML, Coates PM, et al. (1985) Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of nonketotic hypoglycemia. Pediatr Res 19: 666–671PubMedGoogle Scholar
  2. 11.
    Naylor EW, Mosovidi LL, Guthrie R, et al. (1980) Intermittent non-ketotic dicarboxylic aciduria in two siblings with hypoglycemia: an apparent defect in f-oxidation of fatty acids. J Inherited Metab Dis 3: 19–24PubMedCrossRefGoogle Scholar

SCAD Deficiency

  1. 12.
    Coates PM, Hale DE, Finochiarro G, et al. (1988) Genetic deficiency of short-chain acylCoA dehydrogenase in cultured fibroblasts from a patient with muscle carnitine deficiency and severe skeletal muscle weakness. J Clin Invest 81: 171–175PubMedCrossRefGoogle Scholar

3-OH ACD Deficiency

  1. 13.
    Hale DE (1989) The L-3-hydroxy acyl-CoA dehydrogenase deficiency. In: Tanaka K, Coates PM (eds) Clinical, biochemical, and molecular aspects of fatty acid oxidation. Liss, New York pp 503–510Google Scholar

MAD Deficiency

  1. 14.
    Frerman FE, Goodman SI (1985) Deficiency of electron transfer flavoprotein or electron transfer flavoprotein: ubiquinone oxidoreductase in glutaric acidemia type II fibroblasts. Proc Natl Acad Sci USA 82: 4517–4520PubMedCrossRefGoogle Scholar
  2. 15.
    Dusheiko G, Kew MC, Joffe BI, et al. (1979) Recurrent hypoglycemia associated with glutaric aciduria type II in an adult. N Engl J Med 301: 1405–1409PubMedCrossRefGoogle Scholar
  3. 16.
    Amendt BA, Rhead WJ (1986) The multiple acyl coenzyme A dehydrogenation disorders, glutaric aciduria type Il and ethylmalonic-adipic aciduria. J Clin Invest 78: 205–213PubMedCrossRefGoogle Scholar

Primary Carnitine Deficiency

  1. 17.
    Treem WR, Stanley CA, Finegold DN, et al. (1988) Primary carnitine deficiency due to a failure of carnitine transport in kidney, muscle, and fibroblasts. N Engl J Med 319: 1331–1336PubMedCrossRefGoogle Scholar
  2. 18.
    Waber Li, Valle D, Neill C, et al. (1982) Carnitine deficiency presenting as familial cardiomyopathy: a treatable defect in carnitine transport. J Pediatr 101: 700–705CrossRefGoogle Scholar

CPT Deficiency

  1. 19.
    Demaugre F, Bonnefon JP, Mitchell G, et al. (1988) Hepatic and muscular presentation of carnitine palmitoyl transferase deficiency: two distinct entities. Pediatr Res 24: 308–311PubMedCrossRefGoogle Scholar
  2. 20.
    DiMauro S, DiMauro PM (1973) Muscle carnitine palmityltransferase deficiency and myoglobinuria. Science 182: 929–931PubMedCrossRefGoogle Scholar

HMG-CoA Lyase Deficiency

  1. 21.
    Robinson BH, Oei J, Sherwood WG, et al. (1980) Hydroxymethylglutaryl CoA lyase deficiency: features resembling Reye syndrome. Neurology (NY) 30: 714–718CrossRefGoogle Scholar
  2. 22.
    Roe CR, Millington DS, Maltby DA (1986) Identification of 3-methylglutaryl-carnitine. A new diagnostic metabolite of 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency. J Clin Invest 77: 1391–1399PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

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  • C. A. Stanley

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