SYNTHESIS AND CHARACTERIZATION OF ACYL GLYCINES - THEIR MEASUREMENT IN SINGLE BLOOD SPOTS BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY TO DIAGNOSE INBORN-ERRORS OF METABOLISM

Acyl glycines are normally minor metabolites of fatty acids; however, the excretion of certain acyl glycines is increased in several inborn errors of metabolism. Therefore measurement of these metabolites in bo dy fluids can be used to diagnose these metabolic disorders. The chemi cal synthesis of a range of acyl glycines is described, together with that of their C-13(2)-isotopomers for use as internal standards. An an alytical method for the measurement of hexanoyl, octanoyl, 3-phenylpro pionyl and suberyl glycines in urine, employing gas chromatography-mas s spectrometry with negative-ion chemical ionisation was adapted to me asure a larger range of acyl glycines in a single blood spot on a stan dard Guthrie card. Diagnoses of a case of medium-chain acyl-CoA dehydr ogenase deficiency and a case of isovaleric acidaemia were confirmed u sing a single blood spot from each patient.