The Clinical Chemome: A Tool for the Diagnosis and Management of Chronic Disease

Garrod was among the first to recognize the importance of genetics as a determinant of disease. In his Croonian Lecture in 1908, he introduced the term “inborn errors of metabolism”, long before the nature of genes, proteins, and enzymes was understood. Numerous recent articles in Clinical Chemistry have focused on the application of modern mass spectrometry to the analysis of metabolites in plasma or urine for diagnosis of genetic diseases resulting from defects in single enzymes or transport systems. Novel liquid chromatography–mass spectrometry (LC/MS) methodologies, supported by bioinformatics and pattern-recognition algorithms, are also being developed for “omic” analysis and diagnosis of disease, including “genomics” (genetic complement), “transcriptomics” (gene expression), “proteomics” (protein synthesis and signaling), “metabolomics” (concentrations and fluxes of cellular metabolites), and “metabonomics” (systemic profiling by analysis of biological fluids) (1).The more common, noninfectious diseases in the modern world, such as cancer, diabetes, and cardiovascular and neurodegenerative diseases, do not fit into Garrod’s construct—that a deficiency in a single enzyme leads to a single disease entity. These and other chronic, age-related diseases are multifactorial and multigene in origin and often have a substantial nonenzymatic, nonmetabolic, chemical component. Chemical modification of proteins, often as a result of oxidative stress mediated by reactive oxygen …