3-Hydroxyisovalerylcarnitine in patients with deficiency of 3-methylcrotonyl CoA carboxylase

Wulf Röschinger, David S. Millington, Douglas A. Gage, Zhi H. Huang, Takeo Iwamoto, Shoji Yano, Seymour Packman, Kay Johnston, Susan A Berry, Lawrence Sweetman

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Highly elevated urinary acylcamitine levels (range: 27.1-1314.0; normal: <30 mmol/mol creatinine) combined with a generalized, severe decrease of free carnitine before treatment in six patients of two families with an isolated biotin-unresponsive deficiency of 3-methylcrotonyl CoA:carboxylase (3-methylcrotonyl-CoA:carbon dioxide ligase; EC prompted the study to specify the acyl moities attached to the carrier molecule carnitine. Only traces of 3-methylcrotonyl carnitine (1.3-2.2% of total ester concentration) were found by high performance liquid chromatography, whereas the prominent species determined by fast-atom bombardment/tandem mass spectrometry and gas chromatography-mass spectrometry corresponded to a hydroxy five-carbon-acylcamitine. Crude urine samples were derivatized directly and the resulting N-demethylcamitine-propylester and trimethylsilylesters/ethers of intact acylcarnitines analyzed by gas chromatography-mass spectrometry. Mass spectra acquired by both chemical ionization and electron impact gave both the molecular weight and fragmentation patterns consistent with that expected for 3-hydroxyisovaleryl carnitine. In addition, acylcarnitines were extracted from urine, hydrolyzed and the trimethylsilyl-derivatives of the organic acids analyzed by gas chromatography-mass spectrometry. Free 3-hydroxyisovaleric acid found in the hydrolyzed sample and not in an unhydrolyzed one confirmed the suggested acyl group.

Original languageEnglish (US)
Pages (from-to)35-51
Number of pages17
JournalClinica Chimica Acta
Issue number1
StatePublished - Aug 31 1995

Bibliographical note

Funding Information:
W.R. was supportedb y the DeutscheF orschungsgemcinsch(aRfot 763/1-2), whichi s gratefullya cknowledgeSdo. meo f the masss pectradl ataw crca cquireda t the MSU-NIH Mass SpectrometrFya cilityw hichi s supportedin, part, by a grant (RR00480f)r om the NationalI nstituteso f Health,N ationalC enterf or Research Resources.


  • 3-Hydroxyisovalerylcamitine
  • 3-Methylcrotonyl CoA carboxylase
  • Acylcamitine


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