Journal of Inherited Metabolic Disease

, Volume 37, Issue 4, pp 541–551 | Cite as

Ketone body metabolism and its defects

  • Toshiyuki FukaoEmail author
  • Grant Mitchell
  • Jörn Oliver Sass
  • Tomohiro Hori
  • Kenji Orii
  • Yuka Aoyama
ICIEM Symposium 2013


Acetoacetate (AcAc) and 3-hydroxybutyrate (3HB), the two main ketone bodies of humans, are important vectors of energy transport from the liver to extrahepatic tissues, especially during fasting, when glucose supply is low. Blood total ketone body (TKB) levels should be evaluated in the context of clinical history, such as fasting time and ketogenic stresses. Blood TKB should also be evaluated in parallel with blood glucose and free fatty acids (FFA). The FFA/TKB ratio is especially useful for evaluation of ketone body metabolism. Defects in ketogenesis include mitochondrial HMG-CoA synthase (mHS) deficiency and HMG-CoA lyase (HL) deficiency. mHS deficiency should be considered in non-ketotic hypoglycemia if a fatty acid beta-oxidation defect is suspected, but cannot be confirmed. Patients with HL deficiency can develop hypoglycemic crises and neurological symptoms even in adolescents and adults. Succinyl-CoA-3-oxoacid CoA transferase (SCOT) deficiency and beta-ketothiolase (T2) deficiency are two defects in ketolysis. Permanent ketosis is pathognomonic for SCOT deficiency. However, patients with “mild” SCOT mutations may have nonketotic periods. T2-deficient patients with “mild” mutations may have normal blood acylcarnitine profiles even in ketoacidotic crises. T2 deficient patients cannot be detected in a reliable manner by newborn screening using acylcarnitines. We review recent data on clinical presentation, metabolite profiles and the course of these diseases in adults, including in pregnancy.


AcAc Ketone Body Urinary Organic Acid Urinary Organic Acid Analysis Total Ketone Body 
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.



We thank the many physicians who have referred samples and shared clinical data of patients suspected to be deficient in T2 or SCOT. This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and Health and Labor Science Research Grants for Research on Intractable Diseases from the Ministry of Health, Labor and Welfare of Japan.

Compliance with Ethics Guidelines

Conflict of Interest


Human and Animal Rights and Informed Consent

This is a review article, hence, this article does not contain any studies with human or animal subjects performed by any of the authors.


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Copyright information

© SSIEM and Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Toshiyuki Fukao
    • 1
    • 2
    Email author
  • Grant Mitchell
    • 3
  • Jörn Oliver Sass
    • 4
  • Tomohiro Hori
    • 1
  • Kenji Orii
    • 1
  • Yuka Aoyama
    • 2
  1. 1.Department of PediatricsGraduate School of Medicine, Gifu UniversityGifuJapan
  2. 2.Medical Information Sciences DivisionUnited Graduate School of Drug Discovery and Medical Information Sciences, Gifu UniversityGifuJapan
  3. 3.Division of Medical Genetics, Department of PediatricsCHU Sainte-Justine and Université de MontréalMontrealCanada
  4. 4.Division of Clinical Chemistry & BiochemistryUniversity of Zurich Children’s HospitalZurichSwitzerland

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