Clinical Metabolomics: The New Metabolic Window for Inborn Errors of Metabolism Investigations in the Post-Genomic Era

Abstract

Inborn errors of metabolism (IEM) represent a group of about 500 rare genetic diseases with an overall estimated incidence of 1/2500. The diversity of metabolic pathways involved explains the difficulties in establishing their diagnosis. However, early diagnosis is usually mandatory for successful treatment. Given the considerable clinical overlap between some inborn errors, biochemical and molecular tests are crucial in making a diagnosis. Conventional biological diagnosis procedures are based on a time-consuming series of sequential and segmented biochemical tests. The rise of "omic" technologies offers holistic views of the basic molecules that build a biological system at different levels. Metabolomics is the most recent "omic" technology based on biochemical characterization of metabolites and their changes related to genetic and environmental factors. This review addresses the principles underlying metabolomics technologies that allow them to comprehensively assess an individual biochemical profile and their reported applications for IEM investigations in the precision medicine era.

Keywords: diagnosis; inborn errors of metabolism; metabolomics; precision medicine; screening; systems medicine.

Figure 1

Translational metabolomics workflow.

Figure 2

Clinical metabolomics implementation strategies.

Figure 3

Metabolomics challenges for effective clinical implementation.

Figure 4

Paradigm shift in Inborn Errors of Metabolism diagnosis workflow. The change in molecular information recovery in laboratory investigation workflow is driven by advancing analytical technologies and bioinformatics systems for a more effective medical practice using an integrative computational framework. IEM: Inborn Errors of Metabolism.