Proton NMR spectroscopic analysis of multiple acyl-CoA dehydrogenase deficiency-capacity of the choline oxidation pathway for methylation in vivo

Proton NMR spectra of urine from subjects with multiple acyl-CoA dehydrogenase deficiency, caused by defects in either the electron transport flavoprotein or electron transport flavoprotein ubiquinone oxidoreductase, provide a characteristic and possibly diagnostic metabolite profile. The detection of dimethylglycine and sarcosine, intermediates in the oxidative degradation of choline, should discriminate between multiple acyl-CoA dehydrogenase deficiency and related disorders involving fatty acid oxidation, The excretion rates of betaine, dimethylglycine (and sarcosine) in these subjects give an estimate of the minimum rates of both choline oxidation and methyl group release from betaine and reveal that the latter is comparable with the calculated total body methyl requirement in the human infant even when choline intake is very low. Our results provide a new insight into the rates of in vivo methylation in early human development. (C) 1998 Elsevier Science B.V. All rights reserved.