The most common concern for neonates who present with poor feeding, tachypnea, hypothermia, and lethargy during the first days of life is sepsis; in fact, this is the most likely cause of severe illness. However, it is important to also consider the possibility of an inborn error of metabolism. Although individually these are rare disorders, as a group they probably are present in more than 1 in 5000 live births1; if they are not identified early, most die or are left with severe brain damage.
Many inborn errors that present in the newborn period with a catastrophic illness have elevated ammonia levels as a presenting symptom. It is our recommendation that every neonate who is worked up for sepsis should also have a plasma ammonia level drawn. While expanded newborn screening has been helpful in diagnosing a number of causes of neonatal hyperammonia, the results are often not available until the outcome of the disease is unalterable. At best, they become available when the child is showing symptoms and may aid in making the diagnosis. In this chapter, we discuss the clinical presentation, laboratory evaluation, and clinical effects of neonatal hyperammonemia. Chapter 106 provides a clinical management template for intervention in neonatal hyperammonemia.
DEFINING HYPERAMMONEMIA AND OBTAINING A SPECIMEN
Typical plasma ammonia levels in neonates are less than 40 μmol/L, similar to that in older children and adults. Premature infants may have somewhat higher levels (in the range of 40–60 μmol/L) because of the immaturity of their liver function and lower production of arginine during the first few weeks of life.2 Clinical symptoms attributable to hyperammonemia in the newborn generally occur above levels of 150 μmol/L, and it is not uncommon for neonates with urea cycle disorders to have plasma ammonia levels in the 1000–2000 μmol/L range.
The measurement of plasma ammonia can be affected by the collection technique, so a free-flowing sample is recommended. Plasma, once obtained, should immediately be placed on ice, taken to the laboratory, and analyzed within 30 minutes. With delayed measurement after sample collection, glutamine is deaminated to glutamate, which can lead to false elevation of plasma ammonia. Levels of plasma ammonia over 200 μmol/L in the neonate are highly suggestive of an underlying inborn error of metabolism and require immediate intervention.
CLINICAL PRESENTATION OF HYPERAMMONEMIA IN THE NEONATE
The classic presentation of neonatal hyperammonemia is as a catastrophic illness in the first week of life. Signs and symptoms of hyperammonia in the neonate depend on the proximate cause and the rapidity of ammonia accumulation. In patients with rapidly accumulating ammonia, presentation may occur in the first 2–3 days of life with lethargy and poor feeding. This may progress over a matter of hours to temperature instability, coma, and evidence of increased intracranial pressure. With more indolent ammonia accumulation, initial presentation ...