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Inherited Metabolic Diseases pp 461–487Cite as

Enzyme Diagnostics in a Changing World of Exome Sequencing and Newborn Screening as Exemplified for Peroxisomal, Mitochondrial, and Lysosomal Disorders

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Abstract

Enzymes are the ultimate catalysts of chemical reactions and thus form the essence of metabolic pathways to ensure metabolic homeostasis. This occurs in close conjunction with the multiple transmembrane metabolite transporters which allow enzymes localized in different compartments within each individual cell to interact with one another. Until recently, enzymology was the obligatory, second step in the diagnostic algorithm aimed to identify the underlying defect in any patient suspected to suffer from an inborn error of metabolism (IEM) as a logical follow-up of metabolic investigations. This classical approach has led to the discovery of numerous inborn errors of metabolism. The introduction of sophisticated, highly accurate, and fast DNA sequencing technologies has revolutionized the field of inborn errors of metabolism and DNA sequencing may soon be the first line of investigation, especially in patients with an undefined set of signs and symptoms. Although these new developments will definitely change the sequence of events in the diagnosis of patients suspected to suffer from an inborn error of metabolism, enzymological studies will remain of crucial importance since it is the only way to resolve the functional consequences of the DNA variants found upon whole exome or whole genome sequencing in close conjunction with metabolite studies in such patients. We will describe the importance of enzymology for the diagnosis of patients affected by a peroxisomal disorder, a disorder of mitochondrial beta-oxidation, a defect in oxidative phosphorylation (OXPHOS), or a lysosomal disorder.

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Authors and Affiliations

  1. Laboratory of Genetic Metabolic Diseases, Academic Medical Centre, University of Amsterdam, Room F0-226, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands

    Ronald J. A. Wanders & Ben J. H. M. Poorthuis

  2. Department of Pediatrics, 774 Translational Metabolic Laboratory, Radboud Center for Mitochondrial Medicine, Radboud University Medical Center, Nijmegen, The Netherlands

    Richard J. T. Rodenburg

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  1. Ronald J. A. Wanders
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  2. Ben J. H. M. Poorthuis
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  3. Richard J. T. Rodenburg
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Correspondence to Ronald J. A. Wanders .

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Editors and Affiliations

  1. Department of Pediatrics, University of Heidelberg, Heidelberg, Germany

    Georg F. Hoffmann

  2. Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria

    Johannes Zschocke

  3. Department of Pediatrics, University of California San Diego , La Jolla, California, USA

    William L. Nyhan

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Wanders, R.J.A., Poorthuis, B.J.H.M., Rodenburg, R.J.T. (2017). Enzyme Diagnostics in a Changing World of Exome Sequencing and Newborn Screening as Exemplified for Peroxisomal, Mitochondrial, and Lysosomal Disorders. In: Hoffmann, G., Zschocke, J., Nyhan, W. (eds) Inherited Metabolic Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-49410-3_38

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