Application of mass spectrometry and metabolite profiling to the study of human diseases

Abstract

Many human diseases result in characteristic changes in the biochemical composition of the cells and the body fluids. The profiling approach, with gas chromatography-mass spectrometry (g.c.-m.s.) and computer handling of the data, are suitable for detecting such changes, e.g. the production of abnormal metabolites in a patient. The methods can be used to diagnose and study about 100 different metabolic disorders, and have resulted in the discovery of 25 new inborn errors of metabolism. Other diseases, such as ketoacidosis, lactic acidosis, bacterial and viral infections, rheumatoid arthritis and cancer, are currently studied by means of g.c.-m.s. methods. Many difficulties and pitfalls are attached to the investigation of human diseases by g.c.-m.s. Dietary variation, drug intake and artefacts produced during chemical pretreatment of the samples, and lack of knowledge of the normal constituents seen in the various profiles, are factors to consider. Despite many problems, the methods have proved to be valuable analytical tools in the clinical laboratory. It is likely that the new developments in mass spectrometry technology (e.g. automatic computer evaluation of the g.c. profiles, automated pyrolysis-m.s., high resolution g.c.-m.s.) will make the methods play increasingly important roles in the biomedical field.