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Inborn errors of metabolism: Identifying the specific disorder

V Reid Sutton, MD
Section Editor
Sihoun Hahn, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS


Optimal outcome for children with inborn errors of metabolism (IEM) depends upon recognition of the signs and symptoms of metabolic disease, prompt evaluation, and referral to a center familiar with the evaluation and management of these disorders [1]. Delay in diagnosis may result in acute metabolic decompensation, progressive neurologic injury, or death.

This topic provides an overview of the evaluation for children with suspected IEM. Confirmation of diagnosis of specific disorders typically requires specialized testing and should be undertaken in consultation with a specialist in genetics or metabolic diseases. The classification, most common presentations, and initial evaluation and management of IEM, particularly those that present as metabolic emergencies, are discussed separately, as are individual disorders. (See "Inborn errors of metabolism: Classification" and "Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features" and "Inborn errors of metabolism: Metabolic emergencies".)


A newborn may present with a positive newborn screen for IEM before clinical manifestations are present or recognized. Newborn screening programs screen all newborns for a specific set of IEM [2]. The testing methods and disorders that are screened vary from state to state and country to country. (See "Newborn screening".)

Newborn screening programs increase the detection of IEM but cannot be relied upon exclusively. False-positive and false-negative screening tests occur, usually as a result of screening too early (ie, before adequate "challenge" with protein or carbohydrate), medications, and/or transfusions [3,4]. In addition, the results of the screening tests may not be available in the first few days of life, when some IEM may present. Furthermore, newborn screening programs do not screen for all IEM. As an example, the urea cycle disorders ornithine transcarbamylase deficiency and carbamoylphosphate synthetase deficiency are not detected by available newborn screening methods. Improved detection depends upon a high index of suspicion. Guidelines for evaluation following an abnormal newborn screen can be found in ACTion (ACT) sheets from the American College of Medical Genetics. These guidelines and other helpful information are also often available from the state newborn screening program (including postings on their websites). (See "Newborn screening".)


The history should focus on previous episodes of metabolic decompensation, identification of potential triggering events, and family history of metabolic disease or members with similar presentations.

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Literature review current through: Nov 2017. | This topic last updated: Nov 28, 2017.
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