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Metabolic Diseases in Hyperammonemic Newborns

Metabolic Diseases in Hyperammonemic Newborns is a topic covered in the Select 5-Minute Pediatrics Topics.

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  • Inborn errors of metabolism are inherited defects in biochemical pathways affecting metabolism of fats, amino acids, or carbohydrates.
  • Some inborn errors of metabolism present with elevated ammonia in newborns (>100 micromolar). Because these conditions are life-threatening if not treated promptly, maintaining a high degree of clinical suspicion in sick neonates is essential. In the newborn period, the immediate goals include:
    • Establish a tentative diagnosis.
    • Initiate presumptive management.
    • Send confirmatory studies.
    • Involve a team trained in treating patients with inborn errors of metabolism.

Risk Factors


Generally autosomal recessive. Ornithine transcarbamylase deficiency (the most common urea cycle defect) is X-linked. Incidence of urea cycle defects is ∼1 in 45,000 births.


The urea cycle coverts ammonia (NH3) to water-soluble urea in the liver and is the major mechanism for ammonia disposal. Inborn errors of metabolism causing hyperammonemia interfere with urea cycle function, either directly or indirectly, including the following mechanisms:

  • Genetic defects in a urea cycle enzyme per se
  • Decreased production, increased use, or defective transport of a urea cycle intermediate. Examples:
    • Hyperornithinemia, hyperammonemia, homocitrullinemia (HHH) syndrome
    • Lysinuric protein intolerance
    • Fatty acid oxidation defects
    • Hyperammonemia/Hyperinsulinemia syndrome
    • Organic acidemias
    • Pyruvate carboxylase deficiency
  • Hepatotoxicity (galactosemia, hereditary fructose intolerance)

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