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Inborn errors of metabolism: Metabolic emergencies

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


Inborn errors of metabolism (IEM) can present as acute metabolic emergencies resulting in significant morbidity, progressive neurologic injury, or death. As a result, optimal outcome for children with 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 presentation, initial evaluation, and management of children with suspected IEM who present with acute metabolic decompensation. Confirmation of diagnosis of specific disorders typically requires specialized testing and should be undertaken in consultation with a specialist in genetics or metabolic diseases. Determination of the specific IEM is reviewed separately. The classification and most common chronic presentations of IEM are also 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: Identifying the specific disorder".)


IEM can be grouped into disorders of intermediary metabolism (classic IEM), disorders of biosynthesis and breakdown of complex molecules, and disorders of neurotransmitter metabolism (table 1). Many of the disorders of intermediary metabolism can present with acute, life-threatening illness, particularly organic acidurias, urea cycle disorders, maple syrup urine disease, and fatty acid oxidation disorders. Neurotransmitter defects and related disorders can present with severe metabolic encephalopathy. In contrast, the disorders involving complex molecules tend to progress more slowly and do not typically cause acute metabolic decompensation. (See "Inborn errors of metabolism: Classification", section on 'Classification'.)

Metabolic crises occur when there is build-up of toxic metabolites. Triggers include factors that cause increased catabolism (acute infection; surgery, trauma, or even the birthing process; fasting) or increased consumption of a food component (eg, increased protein intake when switching from breast milk to cow's milk). Acute metabolic decompensation typically occurs after a period of apparent well-being. The duration of the symptom-free period may range from hours to months and sometimes years. (See "Inborn errors of metabolism: Identifying the specific disorder", section on 'Clinical evaluation' and "Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features", section on 'Age at presentation'.)

As an example, episodic metabolic decompensation with poor intake or fasting may be a feature of carbohydrate disorders, fatty acid oxidation disorders, and certain amino acid disorders. In many cases, the severity of decompensation may seem out of proportion to the precipitating condition (eg, mild gastroenteritis resulting in severe dehydration necessitating hospitalization for intravenous fluids or recurrent episodes of hypoglycemia in a school-aged child) [2,3].

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Literature review current through: Nov 2017. | This topic last updated: Oct 20, 2017.
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