Inborn Errors of Metabolism (Metabolic Disorders)

Gregory M. Rice; Robert D. Steiner

doi:10.1542/pir.2014-0122

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Gregory M. Rice, MD*
Robert D. Steiner, MD*,^†

^*Department of Pediatrics and the Waisman Center, University of Wisconsin School of Medicine and Public Health, Madison, WI.
^†Marshfield Clinic Research Foundation, Marshfield, WI.

AUTHOR DISCLOSURE
Dr Rice has disclosed that he is a site principal investigator for BioMarin Pharmaceutical and that he is a collaborator on and receives support from FDA grant R01 FD003711-01A1. Dr Steiner has disclosed no financial relationships relevant to this article. This commentary does contain a discussion of an unapproved/investigative use of a commercial product/device.

Educational Gaps

Clinicians should be able to recognize the proper metabolic laboratory testing to evaluate for a suspected inborn error of metabolism.
Clinicians should recognize the common presentations and treatments of inborn errors of metabolism.

Objectives

After completing this article, readers should be able to:

Use basic and specific laboratory tests to aid in the diagnosis of metabolic disease.
Understand the capabilities and limitations of modern newborn screening approaches.
Recognize that urea cycle disorders can result in hyperammonemia, which is a medical emergency that requires prompt diagnosis and treatment.
Develop a basic framework for understanding inborn errors of metabolism to aid in recognition and diagnosis of these conditions.
Appreciate that although most classic metabolic disorders present in infancy, most conditions can also present with milder variants later in life.

Introduction

Metabolic disorders can appear to be a frustratingly complex group of disorders to master. Many individual disorders have clinical presentations that initially seem very similar to one another. In addition, classification systems can be difficult to apply because of the multitude and variety of metabolic pathways involved. This review serves as an update of previously published information (1)(2)(3) and attempts to impose a basic classification framework and diagnostic approach that can be applied by the general pediatrician or primary pediatric clinician in the initial triage and identification of metabolic diseases.

The classification groups disorders into those caused by defects in the metabolism of energy sources (lipids, proteins, or carbohydrate) and those caused by dysfunction …