The laboratory diagnosis of inborn errors of metabolism has been revolutionized in recent years, thanks to the amazing developments in the field of DNA sequencing including whole exome and whole genome sequencing (WES and WGS). Interpretation of the results coming from WES and/or WGS analysis is definitely not trivial especially since the biological relevance of many of the variants identified by WES and/or WGS, have not been tested experimentally and prediction programs like POLYPHEN-2 and SIFT are far from perfect. Correct interpretation of WES and/or WGS results can only be achieved by performing functional studies at multiple levels (different metabolomics platforms, enzymology, in vitro and in vivo flux analysis), often requires studies in model organisms like zebra fish, Caenorhabditis elegans, Saccharomyces cerevisiae, mutant mice and others, and also requires the input of many different disciplines to make this Translational Metabolism approach effective.
Wanders, R. J. A., Vaz, F. M., Ferdinandusse, S., van Kuilenburg, A. B. P., Kemp, S., van Karnebeek, C. D., ... Houtkooper, R. H. (2019). Translational Metabolism: A multidisciplinary approach towards precision diagnosis of inborn errors of metabolism in the omics era. Journal of Inherited Metabolic Disease, 42(2), 197-208. https://doi.org/10.1002/jimd.12008