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Disorders of Ketogenesis and Ketolysis

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Inborn Metabolic Diseases

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Abstract

Disorders of ketone body metabolism present either in the first few days of life or later in childhood, during an infection or some other metabolic stress. In defects of ketogenesis, decompensation leads to encephalopathy, with vomiting and a reduced level of consciousness, often accompanied by hepatomegaly. The biochemical features – hypoketotic hypoglycaemia, with or without hyperammonaemia – resemble those seen in fatty acid oxidation disorders. In defects of ketolysis, the clinical picture is dominated by severe ketoacidosis. This is often accompanied by decreased consciousness and dehydration.

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References

  1. Thompson GN, Hsu BY, Pitt JJ et al. (1997) Fasting hypoketotic coma in a child with deficiency of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase. N Engl J Med 337:1203–1207

    Article  PubMed  CAS  Google Scholar 

  2. Zschocke J, Penzien JM, Bielen R et al. (2002) The diagnosis of mitochondrial HMG-CoA synthase deficiency. J Pediatr 140:778–780

    Article  PubMed  CAS  Google Scholar 

  3. Aledo R, Mir C, Dalton RN et al. (2006) Refining the diagnosis of mitochondrial HMG-CoA synthase deficiency. J Inherit Metab Dis 29:207–211

    Article  PubMed  CAS  Google Scholar 

  4. Gibson KM, Breuer J, Nyhan WL (1988) 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: review of 18 reported patients. Eur J Pediatr 148:180–186

    Article  PubMed  CAS  Google Scholar 

  5. Knaap v d MS, Bakker HD, Valk J (1998) MR imaging and proton spectroscopy in 3-hydroxy-3-methylglutaryl coenzyme A lyase deficiency. AJNR Am J Neuroradiol 19:378–382

    Google Scholar 

  6. Reimao S, Morgado C, Almeida IT et al. (2009) 3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: initial presentation in a young adult. J Inherit Metab Dis Short report nr 152 published on line

    Google Scholar 

  7. Ozand PT, al Aqeel A, Gascon G et al. (1991) 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency in Saudi Arabia. J Inherit Metab Dis 14:174–188

    Article  PubMed  CAS  Google Scholar 

  8. Wilson WG, Cass MB, Sovik O et al. (1984) A child with acute pancreatitis and recurrent hypoglycemia due to 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. Eur J Pediatr 142:289–291

    Article  PubMed  CAS  Google Scholar 

  9. Gibson KM, Cassidy SB, Seaver LH et al. (1994) Fatal cardiomyopathy associated with 3-hydroxy-3-methylglutaryl-CoA lyase deficiency. J Inherit Metab Dis 17:291–294

    Article  PubMed  CAS  Google Scholar 

  10. Berry GT, Fukao T, Mitchell GA et al. (2001) Neonatal hypoglycaemia in severe succinyl-CoA: 3-oxoacid CoA-transferase deficiency. J Inherit Metab Dis 24:587–595

    Article  PubMed  CAS  Google Scholar 

  11. Saudubray JM, Specola N, Middleton B et al. (1987) Hyperketotic states due to inherited defects of ketolysis. Enzyme 38:80–90

    PubMed  CAS  Google Scholar 

  12. Fukao T, Scriver CR, Kondo N (2001) The clinical phenotype and outcome of mitochondrial acetoacetyl-CoA thiolase deficiency (beta-ketothiolase or T2 deficiency) in 26 enzymatically proved and mutation-defined patients. Mol Genet Metab 72:109–114

    Article  PubMed  CAS  Google Scholar 

  13. Schutgens RB, Middleton B, Blij v d JF et al. (1982) Beta-ketothiolase deficiency in a family confirmed by in vitro enzymatic assays in fibroblasts. Eur J Pediatr 139:39–42

    Article  PubMed  CAS  Google Scholar 

  14. Robinson BH, Sherwood WG, Taylor J et al. (1979) Acetoacetyl CoA thiolase deficiency: a cause of severe ketoacidosis in infancy simulating salicylism. J Pediatr 95:228–233

    Article  PubMed  CAS  Google Scholar 

  15. Henry CG, Strauss AW, Keating JP et al. (1981) Congestive cardiomyopathy associated with beta-ketothiolase deficiency. J Pediatr 99:754–757

    Article  PubMed  CAS  Google Scholar 

  16. Ozand PT, Rashed M, Gascon GG et al. (1994) 3-Ketothiolase deficiency: a review and four new patients with neurologic symptoms. Brain Dev 16 [Suppl]:38–45

    Article  PubMed  Google Scholar 

  17. Kassovska-Bratinova S, Fukao T, Song XQ et al. (1996) Succinyl CoA: 3-oxoacid CoA transferase (SCOT): human cDNA cloning, human chromosomal mapping to 5p13, and mutation detection in a SCOT-deficient patient. Am J Hum Genet 59:519–528

    PubMed  CAS  Google Scholar 

  18. Pie J, Lopez-Vinas E, Puisac B et al. (2007) Molecular genetics of HMG-CoA lyase deficiency. Mol Genet Metab 92:198–209

    Article  PubMed  CAS  Google Scholar 

  19. Hammond J, Wilcken B (1984) 3-Hydroxy-3-methylglutaric, 3-methylglutaconic and 3-methylglutaric acids can be non-specific indicators of metabolic disease. J Inherit Metab Dis 7 [Suppl 2]:117–118

    PubMed  Google Scholar 

  20. Fukao T, Shintaku H, Kusubae R et al. (2004) Patients homozygous for the T435N mutation of succinyl-CoA:3-ketoacid CoA Transferase (SCOT) do not show permanent ketosis. Pediatr Res 56:858–863

    Article  PubMed  CAS  Google Scholar 

  21. Fukao T, Zhang GX, Sakura N et al. (2003) The mitochondrial acetoacetyl-CoA thiolase (T2) deficiency in Japanese patients: urinary organic acid and blood acylcarnitine profiles under stable conditions have subtle abnormalities in T2-deficient patients with some residual T2 activity. J Inherit Metab Dis 26:423–431

    Article  PubMed  CAS  Google Scholar 

  22. Middleton B, Bartlett K (1983) The synthesis and characterisation of 2-methylacetoacetyl coenzyme A and its use in the identification of the site of the defect in 2-methylacetoacetic and 2-methyl-3-hydroxybutyric aciduria. Clin Chim Acta 128:291–305

    Article  PubMed  CAS  Google Scholar 

  23. Wilcken B, Wiley V, Hammond J et al. (2003) Screening newborns for inborn errors of metabolism by tandem mass spectrometry. N Engl J Med 348:2304–2312

    Article  PubMed  CAS  Google Scholar 

  24. Mitchell GA, Jakobs C, Gibson KM et al. (1995) Molecular prenatal diagnosis of 3-hydroxy-3-methylglutaryl CoA lyase deficiency. Prenat Diagn 15:725–729

    Article  PubMed  CAS  Google Scholar 

  25. Fukao T, Wakazono A, Song XQ et al. (1995) Prenatal diagnosis in a family with mitochondrial acetoacetyl-coenzyme A thiolase deficiency with the use of the polymerase chain reaction followed by the heteroduplex detection method. Prenat Diagn 15:363–367

    Article  PubMed  CAS  Google Scholar 

  26. Fukao T, Song XQ, Watanabe H et al. (1996) Prenatal diagnosis of succinyl-coenzyme A:3-ketoacid coenzyme A transferase deficiency. Prenat Diagn 16:471–474

    Article  PubMed  CAS  Google Scholar 

  27. Thompson GN, Chalmers RA, Halliday D (1990) The contribution of protein catabolism to metabolic decompensation in 3-hydroxy-3-methylglutaric aciduria. Eur J Pediatr 149:346–350

    Article  PubMed  CAS  Google Scholar 

  28. Sewell AC, Herwig J, Wiegratz I et al. (1998) Mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase) deficiency and pregnancy. J Inherit Metab Dis 21:441–442

    Article  PubMed  CAS  Google Scholar 

  29. Bennett MJ, Hosking GP, Smith MF et al. (1984) Biochemical investigations on a patient with a defect in cytosolic acetoacetyl-CoA thiolase, associated with mental retardation. J Inherit Metab Dis 7:125–128

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Biochemical Genetics Unit Genetic Medicine Manchester Academic Health Science Centre, University of Manchester Central Manchester University Hospitals NHS Foundation Trust St Mary’s Hospital, Oxford Road Manchester M13 9WL, Manchester, UK

    Andrew A.M. Morris

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  1. Andrew A.M. Morris
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Editors and Affiliations

  1. Department of Neurology Neurometabolic Unit, Hôpital Pitié Salpêtrière 47–83 Boulevard de l’Hôpital, Paris Cedex 13, 75651, Paris, France

    Jean-Marie Saudubray

  2. Laboratory of Physiological Chemistry de Duve Institute, University of Louvain Medical School, Avenue Hippocrate 75/39, 1200, Brussels, Belgium

    Georges van den Berghe

  3. Biochemical Genetics Unit Manchester Academic Health Science Centre, Central Manchester University Hospitals St Mary’s Hospital, Oxford Road, M13 9WL, Manchester, UK

    John H. Walter

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© 2012 Springer-Verlag Berlin Heidelberg

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Morris, A. (2012). Disorders of Ketogenesis and Ketolysis. In: Saudubray, JM., van den Berghe, G., Walter, J.H. (eds) Inborn Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-15720-2_14

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  • DOI: https://doi.org/10.1007/978-3-642-15720-2_14

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-15719-6

  • Online ISBN: 978-3-642-15720-2

  • eBook Packages: MedicineMedicine (R0)

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