More than twenty-five inherited organic acidurias have been identified during the last fifteen years. This remarkable development is due mainly to the introduction of gas chromatography, and gas chromatography combined with mass spectrometry, in paediatric laboratories for
metabolic disease. The chemical approach is determined mainly by physical properties of the
acid, such as their extractability and volatility. Most progress has been made with extractable
acids. The techniques used for derivatization are mentioned, such as trimethylsilylation, methylation and the preparation of asymmetric derivatives for the separation of optical enantiomers. Metabolite patterns may be so characteristic that the underlying
enzyme defect can be deduced. Examples are the
leucine degradation defects, all encountered in the authors' laboratory:
branched-chain ketoaciduria; isovaleric acidaemia;
3-methylcrotonylglycinuria;
3-methylglutaconic aciduria; and
3-hydroxy-3-methylglutaric aciduria. These abnormalities are discussed. D-
glyceric aciduria is shown as an example of a not yet fully understood organic aciduria. The clinical approach varies.
Metabolic acidosis is an indication for organic
acid analysis in urine and plasma, but in many defects there is no
acidosis, or only a transient one caused by secondary metabolites, such as lactic and 3-hydroxybutyric
acids. Gas chromatography is an obligatory routine investigation in screening programmes for
inborn errors of metabolism, especially for the examination of acutely ill neonates and premature babies.