Enantioselective analysis of ketone bodies in patients with beta-ketothiolase deficiency, medium-chain acyl coenzyme A dehydrogenase deficiency and ketonemic vomiting

J Chromatogr B Biomed Sci Appl. 2000 Mar 10;739(2):313-24. doi: 10.1016/s0378-4347(00)00022-0.


Enantioselective multidimensional gas chromatography-mass spectrometry (enantio-MDGC-MS) is a valuable tool for the differentiation of enantiomers from complex matrices when present in trace amounts. The separation of chiral compounds provides further information on the diagnosis of diseases, and on normal and abnormal biochemical pathways. The formation of the normal urinary metabolite 3-hydroxy-2-methylbutanoic acid (HMBA), excreted in abnormally high amounts in beta-ketothiolase deficiency, is not absolutely clarified. Metabolic pathways involving this metabolite are isoleucine catabolism, as well as presumably beta-oxidation of fatty acids and ketogenesis. The latter two pathways are distinguishable in their enantioselectivity. Enantioselective analysis gives further information on interfering metabolic pathways and the selectivity of the enzyme(s) forming HMBA. Different ratios of the stereoisomers of HMBA in control urine samples and patients with beta-ketothiolase deficiency were detected. Analogous to HMBA urinary 3-hydroxybutanoic acid (HBA) was investigated in several diseases. The formation of HBA and HMBA is expected to result from the same or similar metabolic pathways. Differences in the enantiomeric ratio of HMBA may originate from the enantioselectivity of different enzyme systems.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetyl-CoA C-Acyltransferase / deficiency*
  • Acyl-CoA Dehydrogenase
  • Child
  • Fatty Acid Desaturases / deficiency*
  • Gas Chromatography-Mass Spectrometry / methods
  • Humans
  • Ketone Bodies / metabolism*
  • Male
  • Metabolism, Inborn Errors / complications
  • Metabolism, Inborn Errors / metabolism*
  • Oxidation-Reduction
  • Vomiting / etiology
  • Vomiting / metabolism*


  • Ketone Bodies
  • Fatty Acid Desaturases
  • Acyl-CoA Dehydrogenase
  • Acetyl-CoA C-Acyltransferase