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Metabolic emergencies are challenging childhood disorders, often presenting with nonspecific signs and symptoms that may mimic more common conditions such as sepsis. Delay in accurate diagnoses can lead to significant morbidity and mortality, whereas early aggressive management based on probable diagnosis can be lifesaving and reduce long-term neurologic sequelae.
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In any healthy neonate, sudden acute deterioration should prompt consideration of metabolic disease. Vomiting, altered mental status, and poor feeding are the most common clinical features of metabolic emergencies. Appropriate initial management can be started in the ED without definitive diagnosis. This chapter reviews the most common metabolic disorders presenting as acute decompensation in the young infant and the ED treatment. Hypoglycemia is discussed separately. Congenital adrenal insufficiency is included here because of the overlap in presentation with other inherited metabolic disorders and the importance of prompt recognition and treatment in the critically ill neonate. Inherited metabolic disorders that present in later childhood, such as lysosomal storage disease, are often diagnosed and managed outside of the ED, and these disorders are not included here.
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Hypoglycemia is a plasma glucose level of <45 milligrams/dL (2.6 mmol/L) in any symptomatic child or <35 milligrams/dL (<1.9 mmol/L) in an asymptomatic neonate.1,2 Intellectual performance is poor at 18 months in premature infants with persistent serum glucose <47 milligrams/dL,3 and MRI of infants with episodes of hypoglycemia demonstrates patterns of brain injury.4,5,6 This has led to the recommended treatment threshold of 45 milligrams/dL (2.6 mmol/L) for neonates, who may be at higher risk of poor neurologic outcomes than older infants and children.7 Hypoglycemia in children requiring resuscitation is associated with increased mortality, and hypoglycemia in the setting of seizures is associated with poor neurologic outcomes.2,8
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Neonates are born with 60% to 80% of maternal glucose levels. Within 2 to 4 hours, neonates begin to regulate their own serum glucose. Maintenance of serum glucose depends on intake and endogenous gluconeogenesis and glycogenolysis mediated by various hormones. Serum glucose level is affected when there is an imbalance between insulin (hypoglycemic hormone) and its counterregulatory hormones cortisol, growth hormone, glucagon, and epinephrine (hyperglycemic hormones). Insulin stimulates cellular glucose uptake and suppresses lipolysis, whereas hyperglycemic hormones stimulate lipolysis and glycogenolysis. Excess insulin (hyperinsulinemia) results in hypoglycemia with absence of urinary ketones. Hypoglycemia in the neonate or infant may result from inadequate oral intake, excess insulin, deficient hyperglycemic hormones (e.g., growth hormone or adrenal hormone deficiency), disorders of fatty acid oxidation or carbohydrate metabolism, aminoacidopathies and organic acidurias (due to inhibition of gluconeogenesis), or systemic infection (sepsis). Infants of diabetic mothers, postterm infants, and large for gestational age infants are at risk for hypoglycemia due to excess fetal insulin levels in response to elevated maternal serum glucose levels, whereas premature infants or those small for gestational age are at risk due to inadequate glycogen stores.9,10,11