Applications of mass spectrometry in the study of inborn errors of metabolism

During the twentieth century, and particularly in its last decade, there ha ve been major advances in mass spectrometry (MS). As a result, MS remains o ne of the most powerful tools for the investigation of genetic metabolic di sease. Analysis of organic acids by gas chromatography-mass spectrometry (G C-MS) and analysis of acylcarnitines by tandem mass spectrometry are still leading to the discovery of new disorders. Tandem mass spectrometry is incr easingly being used for neonatal screening. New methods for lipid analysis have opened up the fields of inborn errors of cholesterol synthesis, of bil e acid synthesis and of leukotriene synthesis. The latest developments in M S allow it to be used for determination of the amino acid sequence and post translational modifications of proteins. There are still some major hurdles to be overcome, but soon it should be possible to detect mutant proteins d irectly rather than by cDNA or genomic DNA analysis. Measurement of which p roteins are overexpressed and underexpressed ('proteomics') should provide further information on the pathogenesis of complications of inborn errors, e.g. hepatic cirrhosis. The use of stable isotopes in conjunction with MS a llows us to probe metabolic pathways. As an example, evidence is presented to support the contention that vitamin E and its oxidation product are cata bolized by peroxisomal beta -oxidation. Mass spectrometry also has a major role in monitoring new forms of treatment for inborn errors.