Inborn errors of metabolism: Metabolic emergencies
- V Reid Sutton, MD
V Reid Sutton, MD
- Professor of Molecular and Human Genetics
- Baylor College of Medicine
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 . 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".)
CAUSES OF ACUTE METABOLIC DECOMPENSATION
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].To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
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- CAUSES OF ACUTE METABOLIC DECOMPENSATION
- CLINICAL PRESENTATIONS
- Lethargy and coma
- SIDS or ALTE
- LABORATORY FINDINGS
- Acid-base disorders
- INITIAL EVALUATION
- EVALUATION OF SPECIFIC CRITICAL PRESENTATIONS
- Acid-base disorder
- - Metabolic acidosis
- - Respiratory alkalosis
- - Unexplained acid-base disorder
- SIDS and ALTE
- DIFFERENTIAL DIAGNOSIS
- IMMEDIATE MANAGEMENT
- Supportive measures
- Provision of cofactors