PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
 
J Clin Invest. 1987 May; 79(5): 1303–1309.
PMCID: PMC424368

Short-chain acyl-coenzyme A dehydrogenase deficiency. Clinical and biochemical studies in two patients.

Abstract

We describe two patients with short-chain acyl-coenzyme A (CoA) dehydrogenase (SCADH) deficiency. Neonate I excreted large amounts of ethylmalonate and methylsuccinate; ethylmalonate excretion increased after a medium-chain triglyceride load. Neonate II died postnatally and excreted ethylmalonate, butyrate, 3-hydroxybutyrate, adipate, and lactate. Both neonates' fibroblasts catabolized [1-14C]butyrate poorly (29-64% of control). Neonate I had moderately decreased [1-14C]octanoate catabolism (43-60% of control), while neonate II oxidized this substrate normally; both catabolized radiolabeled palmitate, succinate, and/or leucine normally. Cell sonicates from neonates I and II dehydrogenated [2,3-3H]butyryl-CoA poorly (41 and 53% of control) and [2,3-3H]octanoyl-CoA more effectively (59 and 95% of control). Mitochondrial acyl-CoA dehydrogenase (ADH) activities with butyryl- and octanoyl-CoAs were 37 and 56% of control in neonate I, and 47 and 81% of control in neonate II, respectively. Monospecific medium-chain ADH (MCADH) antisera inhibited MCADH activity towards both butyryl- and octanoyl-CoAs, revealing SCADH activities to be 1 and 11% of control for neonates I and II, respectively. Fibroblast SCADH and MCADH activities were normal in an adult female with muscular SCADH deficiency.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Coates PM, Hale DE, Stanley CA, Corkey BE, Cortner JA. Genetic deficiency of medium-chain acyl coenzyme A dehydrogenase: studies in cultured skin fibroblasts and peripheral mononuclear leukocytes. Pediatr Res. 1985 Jul;19(7):671–676. [PubMed]
  • Hale DE, Batshaw ML, Coates PM, Frerman FE, Goodman SI, Singh I, Stanley CA. Long-chain acyl coenzyme A dehydrogenase deficiency: an inherited cause of nonketotic hypoglycemia. Pediatr Res. 1985 Jul;19(7):666–671. [PubMed]
  • Turnbull DM, Bartlett K, Stevens DL, Alberti KG, Gibson GJ, Johnson MA, McCulloch AJ, Sherratt HS. Short-chain acyl-CoA dehydrogenase deficiency associated with a lipid-storage myopathy and secondary carnitine deficiency. N Engl J Med. 1984 Nov 8;311(19):1232–1236. [PubMed]
  • Bennett MJ, Gray RG, Isherwood DM, Murphy N, Pollitt RJ. The diagnosis and biochemical investigation of a patient with a short chain fatty acid oxidation defect. J Inherit Metab Dis. 1985;8 (Suppl 2):135–136. [PubMed]
  • Gregersen N. The acyl-CoA dehydrogenation deficiencies. Recent advances in the enzymic characterization and understanding of the metabolic and pathophysiological disturbances in patients with acyl-CoA dehydrogenation deficiencies. Scand J Clin Lab Invest Suppl. 1985;174:1–60. [PubMed]
  • Mantagos S, Genel M, Tanaka K. Ethylmalonic-adipic aciduria. In vivo and in vitro studies indicating deficiency of activities of multiple acyl-CoA dehydrogenases. J Clin Invest. 1979 Dec;64(6):1580–1589. [PMC free article] [PubMed]
  • Amendt BA, Rhead WJ. The multiple acyl-coenzyme A dehydrogenation disorders, glutaric aciduria type II and ethylmalonic-adipic aciduria. Mitochondrial fatty acid oxidation, acyl-coenzyme A dehydrogenase, and electron transfer flavoprotein activities in fibroblasts. J Clin Invest. 1986 Jul;78(1):205–213. [PMC free article] [PubMed]
  • Rhead WJ, Amendt BA, Fritchman KS, Felts SJ. Dicarboxylic aciduria: deficient [1-14C]octanoate oxidation and medium-chain acyl-CoA dehydrogenase in fibroblasts. Science. 1983 Jul 1;221(4605):73–75. [PubMed]
  • Amendt BA, Rhead WJ. Catalytic defect of medium-chain acyl-coenzyme A dehydrogenase deficiency. Lack of both cofactor responsiveness and biochemical heterogeneity in eight patients. J Clin Invest. 1985 Sep;76(3):963–969. [PMC free article] [PubMed]
  • Duran M, Mitchell G, de Klerk JB, de Jager JP, Hofkamp M, Bruinvis L, Ketting D, Saudubray JM, Wadman SK. Octanoic acidemia and octanoylcarnitine excretion with dicarboxylic aciduria due to defective oxidation of medium-chain fatty acids. J Pediatr. 1985 Sep;107(3):397–404. [PubMed]
  • Rhead WJ, Hall CL, Tanaka K. Novel tritium release assays for isovaleryl-CoA and butyryl-CoA dehydrogenases. J Biol Chem. 1981 Feb 25;256(4):1616–1624. [PubMed]
  • Rhead WJ, Moon A, Roettger V, Henkle K. 14C-labeled substrate catabolism by human diploid fibroblasts derived from infants and adults. Biochem Med. 1985 Oct;34(2):182–188. [PubMed]
  • Moon A, Rhead WJ. Complementation analysis of fatty acid oxidation disorders. J Clin Invest. 1987 Jan;79(1):59–64. [PMC free article] [PubMed]
  • Rhead WJ, Amendt BA. Electron-transferring flavoprotein deficiency in the multiple acyl-CoA dehydrogenation disorders, glutaric aciduria type II and ethylmalonic--adipic aciduria. J Inherit Metab Dis. 1984;7 (Suppl 2):99–100. [PubMed]
  • Thorpe C, Matthews RG, Williams CH., Jr Acyl-coenzyme A dehydrogenase from pig kidney. Purification and properties. Biochemistry. 1979 Jan 23;18(2):331–337. [PubMed]
  • Wendel U. Prenatal detection of defects in propionate metabolism. Clin Chim Acta. 1980 Dec 22;108(3):475–477. [PubMed]
  • Willard HF, Mellman IS, Rosenberg LE. Genetic complementation among inherited deficiencies of methylmalonyl-CoA mutase activity: evidence for a new class of human cobalamin mutant. Am J Hum Genet. 1978 Jan;30(1):1–13. [PubMed]
  • Ikeda Y, Dabrowski C, 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. 1983 Jan 25;258(2):1066–1076. [PubMed]
  • Davidson B, Schulz H. Separation, properties, and regulation of acyl coenzyme A dehydrogenases from bovine heat and liver. Arch Biochem Biophys. 1982 Jan;213(1):155–162. [PubMed]
  • Ikeda Y, Okamura-Ikeda K, Tanaka K. Purification and characterization of short-chain, medium-chain, and long-chain acyl-CoA dehydrogenases from rat liver mitochondria. Isolation of the holo- and apoenzymes and conversion of the apoenzyme to the holoenzyme. J Biol Chem. 1985 Jan 25;260(2):1311–1325. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation