Skip to main content
Log in

Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: A severe fatty acid oxidation disorder

European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

3-Hydroxyacyl-CoA dehydrogenase deficiency is a newly recognised fatty acid oxidation disorder with a usually fatal outcome. We present a further patient who presented with hypoketotic hypoglycaemia, hepatopathy, secondary carnitine deficiency and increased plasma long-chain acylcarnitines. 3-Hydroxydicarboxylic aciduria was present and the diagnosis confirmed in cultured skin fibroblasts. Our patient is compared with those reported in the literature with respect to clinical symptoms, differential diagnosis and possible therapeutic regimens.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abbreviations

CoA :

co-enzyme A

LCAD :

long-chain acyl-CoA dehydrogenase

LCHAD :

long-chain hydroxyacyl-CoA dehydrogenase

MCAD :

medium-chain acyl-CoA dehydrogenase

MCT :

medium-chain triglycerides

SCAD :

short-chain acyl-CoA dehydrogenase

VLCAD :

very long-chain acyl-CoA dehydrogenase

References

  1. Bertini E, Dionisi-Vici C, Garavaglia B, Burlina AB, Sabatelli M, Rimoldi M, Bartuli A, Sabetta G, DiDonato S (1992) Peripheral sensory-motor polyneuropathy, pigmentary retinopathy, and fatal cardiomyopathy in long-chain 3-hydroxy-acyl-CoA dehydrogenase deficiency. Eur J Pediatr 151:121–126

    PubMed  Google Scholar 

  2. Carpenter K, Pollitt RJ, Middelton B (1992) Human liver long-chain 3-hydroxyacyl-coenzyme A dehydrogenase is a multifunctional membrane-bound beta-oxidation enzyme of mitochondria. Biochem Biophys Res Commun: 183:443–448

    PubMed  Google Scholar 

  3. Corr PB, Creer MH, Yamada KA, Saffitz JE, Sobel BE (1989) Prophylaxis of early ventricular fibrillation by inhibition of acylcarnitine accumulation. J Clin Invest 83:927–936

    PubMed  Google Scholar 

  4. Demaugre F, Bonnefont J-P, Brivet M, Cepancec C, Pollitt RJ, Priestly BL, Saudubray J-M, Leroux J-P (1992) Pathophysiological approach to carnitine palmitoyltransferase II deficiencies. In: Coates PM, Tanaka K (eds). Progress in clinical and biological research, vol 375: new developments in fatty acid oxidation. Wiley-Liss, New York, pp 301–309

    Google Scholar 

  5. Dionisi-Vici C, Burlina AB, Bertini E, Bachmann C, Mazziotta MRM, Zacchello F, Sabetta G, Hale DE (1991) Progressive neuropathy and recurrent myoglobinuria in a child with longchain 3-hydroxyacyl-coenzyme A deficiency. J Pediatr 118:744–746

    PubMed  Google Scholar 

  6. Duran M, Wanders RJA, Jager JP de, Dorland L, bruinvis L, Ketting D, Iljist L, Sprang van FJ (1991) 3-Hydroxydicarboxylic aciduria due to long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency associated with sudden neonatal death: protective effect of medium-chain triglyceride treatment. Eur J Pediatr 150:190–195

    PubMed  Google Scholar 

  7. El-Fakhiri M, Middleton B (1979) The existence of two different L-3-hydroxyacyl-coenzyme A dehydrogenases in rat tissues. Biochem Soc Trans 7: 392–393

    PubMed  Google Scholar 

  8. Fischbach PS, Corr PB, Yamada KA (1992) Long-chain acylcarnitine increases intracellular Ca++ and induces after depolarisation in adult ventricular myocytes. Circulation 96:748

    Google Scholar 

  9. Greter J, Lindstedt S, Seeman H, Steen G (1980) 3-Hydroxydecanedioic acid and related homologues: urinary metabolites in ketoacidosis. Clin Chem 26:261–265

    PubMed  Google Scholar 

  10. Hagenfeldt L, Döblen U von, Holme E, Alm J, Brandberg G, Enocksson E, Lindberg L (1990) 3-Hydroxydicarboxylic aciduria — a fatty acid oxidation defect with severe prognosis. J Pediatr 116:387–392

    PubMed  Google Scholar 

  11. Hale DE, Bennett MJ (1992) Fatty acid oxidation disorders: a new class of metabolic diseases. J Pediatr 121:1–11

    PubMed  Google Scholar 

  12. Hale DE, Batshaw ML, Coates PM, Frerman FE, Goodman SI, Singh I, Stanley CA (1985) Long-chain acyl coenzyme A dehydrogenase deficiency. An inherited cause of nonketotic hypoglycemia. Pediatr Res 19: 666–671

    PubMed  Google Scholar 

  13. Hale DE, Thorpe C, Braat K, Wright JH, Roe CR, Coates PM, Hashimoto T, Glasgow AM (1990) The L-3-hydroxyacyl-CoA dehydrogenase deficiency. In: Tanaka K, Coates PM (eds) Fatty acid oxidation: clinical, biochemical and molecular aspects. Alan R. Liss, New York, pp 503–510

    Google Scholar 

  14. Ijlst L, Wanders RJA, Ushikubo S, Kamijo T, Hashimoto T (1993) Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: new information on the mutant protein and first results of mutation analysis. Abstracts of the 31st Symposium SSIEM, Manchester P061

  15. Jackson S, Bartlett K, Land J, Moxon ER, Pollitt RJ, Leonard JV, Turnbull DM (1991) Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. Pediatr Res 29:406–411

    PubMed  Google Scholar 

  16. Moore R, Glasgow JFT, Bingham MA, Dodge JA, Pollitt RJ, Olpin SE, Middleton B, Carpenter K (1993) Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency — diagnosis, plasma carnitine fractions and management in a further patient. Eur J Pediatr 152:433–436

    PubMed  Google Scholar 

  17. Olpin SE, Manning NJ, Carpenter K, Middleton B, Pollitt RJ (1992) Differential diagnosis of hydroxydicarboxylic aciduria based on release of3H2O from [9, 10-3H] myristic and [9, 10-3H] palmitic acids by intact cultured fibroblasts. J Inherited Metab Dis 15:883–891

    PubMed  Google Scholar 

  18. Pollitt RJ (1990) Clinical and biochemical presentations in 20 cases of hydroxydicarboxylic aciduria. In: Tanaka K, Coates PM (eds) Fatty acid oxidation: clinical, biochemical and molecular aspects. Alan R. Liss, New York, pp 495–502

    Google Scholar 

  19. Pollitt RJ, Losty H, Westwood A (1987) 3-Hydroxydicarboxylic aciduria: a distinctive type of intermittent dicarboxylic aciduria of possible diagnostic significance. J Inherited Metab Dis 10 [Suppl 2]:266–269

    Google Scholar 

  20. Poll-The BT, Bonnefont J-P, Ogier H, Charpentier C, Pelet A, Le Fur JM, Jakobs C, Kok RM, Duran M, Divry P, Scotto J, Saudubray J-M (1988) Familial hypoketotic hypoglycaemia associated with peripheral neuropathy, pigmentary retinopathy and C6–C14 hydroxydicarboxylic aciduria. A new defect in fatty acid oxidation? J Inherited Metab Dis 11 [suppl 2]:183–185

    PubMed  Google Scholar 

  21. Ribes A, Riudor E, Navarro C, Boronat M, Marti M, Hale DE (1992) Fatal outcome in a patient with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency. J Inherited metab Dis 15: 278–279

    PubMed  Google Scholar 

  22. Rocchiccioli F, Aubourg P, Bougneres PF (1986) Medium- and long-chain dicarboxylic aciduria in patients with Zellweger syndrome and neonatal adrenoleukodystrophy. Pediatr Res 20: 62–66

    PubMed  Google Scholar 

  23. Rocchiccioli F, Wanders RJA, Aubourg P, Viancy-Liaud C, Ijlst L, Fabre M, Cartier N, Bougneres P-F (1990) Deficiency of long-chain 3-hydroxyacyl-CoA dehydrogenase: a cause of lethal myopathy and cardiomyopathy in early childhood. Pediatr Res 28:657–662

    PubMed  Google Scholar 

  24. Sewell AC, Böhles HJ (1991) 4-Hydroxycyclohexanecarboxylic acid: a rare compound in urinary organic acid analysis. Clin Chem 37:1301–1302

    Google Scholar 

  25. Sewell AC, Herwig J, Böhles HJ, Rinaldo P, Bhala A, Hale DE (1993) A new case of short-chain acyl-CoA dehydrogenase deficiency with isolated ethylmalonic aciduria. Eur J Pediatr 152:922–924

    PubMed  Google Scholar 

  26. Stanley CA (1992) Plasma and mitochondrial membrane carnitine transport defects. In: Coates PM, Tanaka K (eds) Progress in clinical and biological research, Vol 375: new developments in fatty acid oxidation. Wiley-Liss, New York, pp 289–301

    Google Scholar 

  27. Stanley CA, Hale DE, Coates PM, Hall CL, Corkey BE, Yang W, Kelley RI, Gonzales EL, Williamson JR, Baker L (1983) Medium-chain acyl-CoA dehydrogenase deficiency in children with non-ketotic hypoglycaemia and low carnitine levels. Pediatr Res 17: 877–884

    PubMed  Google Scholar 

  28. Treem WR, Witzleben Ca, Piccoli DA, Stanley CA, Hale DE, Coates PM, Watkins JB (1986) Medium-chain and long-chain acyl CoA dehydrogenase deficiency: clinical, pathologic and ultrastructural differentiation from Reye's syndrome. Hepatology 6: 1270–1278

    PubMed  Google Scholar 

  29. Wanders RJA, Ijlst L (1992a) Fatty acid β-oxidation in leukocytes from control subjects and medium-chain acyl-CoA dehydrogenase deficient patients. Biochim Biophys Acta 1138: 80–84

    PubMed  Google Scholar 

  30. Wanders RJA, Ijlst L (1992b) Long-chain 3-hydroxyacyl-CoA dehydrogenase in leukocytes and chorionic villus fibroblasts: potential for pre- and postnatal diagnosis. J Inherited Metab Dis 15:356–358

    PubMed  Google Scholar 

  31. Wanders RJA, Ijlst L, Gennip AH van, Jakobs C, Jager JP de, Dorland L, Sprang FJ van, Duran M (1990) Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of a new inborn error of mitochondrial fatty acid β-oxidation. J Inherited metab Dis 13: 311–314

    PubMed  Google Scholar 

  32. Wanders RJA, Ijlst L, Duran M, Jakobs C, Klerk JBC de, Przyrembel H, Rocchiccioli F, Aubourg P (1991) Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: different clinical expression in three unrelated patients. J Inherited Metab Dis 14:325–328

    PubMed  Google Scholar 

  33. Wanders RJA, Ijlst L, Poggi F, Bonnefont J-P, Munnich A, Brivet M, Rabier D, Saudubray J-M (1992) Human trifunctional protein deficiency: a new disorder of mitochondrial fatty acid oxidation. Biochem Biophys Res Commun 180:1139–1145

    Google Scholar 

  34. Vamecq J, Draye J-P (1989) Comparison between the formation and the oxidation of dicarboxylcarnitine esters in rat liver and skeletal muscle: possible implications for human inborn disorders of mitochondrial β-oxidation. J Inherited Metab Dis 12:58–63

    PubMed  Google Scholar 

  35. Yamaguchi S, Indo Y, Coates PM, Hashimoto T, Tanaka K (1993) Identification of very-long-chain acyl-CoA dehydrogenase deficiency in three patients previously diagnosed with long-chain acyl-CoA dehydrogenase deficiency. Eur J Pediatr 34:111–113

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sewell, A.C., Bender, S.W., Wirth, S. et al. Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: A severe fatty acid oxidation disorder. Eur J Pediatr 153, 745–750 (1994). https://doi.org/10.1007/BF01954492

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01954492

Key words

Navigation