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Inborn errors of metabolism (IEMs), although rare, are becoming more recognized in pediatrics.
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Common examples of inborn errors of metabolism are shown in Table 74-1.
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Newborn screening tests have aided clinicians in diagnosing most of these disorders shortly after birth. However, some infants and children will present later in life, and it is crucial for pediatric ICU providers to recognize these disorders quickly so treatment can be initiated.
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Children with undiagnosed metabolic disorders oftentimes present with:
Varying states of shock
Cardiac insufficiency and/or cardiomyopathies
Feeding intolerance, failure to thrive, vomiting, and lethargy
Profound dehydration with or without metabolic acidosis
Altered mental status with or without hyperammonemia
Intractable seizures
Developmental delay
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These predominately autosomal-recessive disorders often result in significant enzyme deficiencies impairing mitochondrial function. Mitochondria therefore:
Cannot break down proper by-products of certain metabolic pathways, which impairs their function on the cellular level
Accumulate dysfunctional upstream metabolites, which becomes toxic to the cell and patient
Shunt metabolites into other pathways, which get overloaded or are unable to process these metabolites
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WORKING UP A METABOLIC DISORDER
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Physicians who suspect an underlying metabolic disorder or a patient in metabolic crisis should immediately evaluate the following on physical exam:
Vital signs: Assess for fever or hypothermia, abnormal changes in blood pressure and pulse pressure, alterations in heart rate and rhythm, and variations in respiratory effort (irregular breathing or large Kussmaul breaths)
General appearance: Observation of coarsened facial features, body odor/smell
Ophthalmologic exam: Consider a distinct eye exam to evaluate for cataracts, changes in retinal pigmentation
Cardiovascular exam: Evaluate for signs of cardiogenic shock; assess for brisk or delayed capillary refill, bounding pulses, displaced point of maximal impulse (PMI), murmurs
Abdominal exam: Direct palpation for hepatosplenomegaly
Neurologic exam: Note baseline Glasgow Coma Score (GCS) for encephalopathy, hypotonia or hypertonia, brisk tendon reflexes, pupillary irregularities, or cranial nerve deficits
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Initial laboratory studies should include the following:
Arterial blood gas to evaluate for changes in blood pH and the presence of metabolic acidosis and lactate production
Rapid blood glucose to evaluate for hypoglycemia
Rapidly run iced ammonia levels on free-flowing blood samples
Basic metabolic panels to assess bicarbonate levels and electrolyte derangements
Pyruvate levels
Blood and urine ketones/β-hydroxybutyrate
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