Spin-echo and 2-dimensional 1H nuclear magnetic resonance studies on urinary metabolites from patients with 2-methylacetocetyl CoA thiolase deficiency

Abstract

Spin-echo 1H nuclear magnetic resonance (nmr) spectra of urine from two unrelated patients with 3-oxoacylthiolase deficiency are presented. The metabolite profile revealed by these spectra is probably of diagnostic value. Two of the major abnormal metabolites known to accumulate in this disorder (tiglylglycine and 2-methyl-3-hydroxybutyrate) can both be detected in the spectra. The technique offers the advantage over combined gas chromatography/mass spectrometry that no pre-treatment of the sample is required and that the data can be obtained in less than 2 min. In addition 2-dimensional nmr techniques (J-resolved and chemical shift correlated) were used to further characterise the spectra. This allowed assignment of resonances which could not be detected in the spin-echo spectra, in particular 2-methylacetoacetate and butanone, which are known to accumulate in this disease.