DESCRIPTION

• Hyperammonemia is a finding in many different inborn errors of metabolism (IEMs) that can present with acute life-threatening encephalopathic crises to milder, nonspecific clinical episodes of malaise, emesis, lethargy, anorexia, or even acute neuropsychiatric abnormalities.
  • Accurate ammonia levels must be obtained from free-flowing samples, placed on ice, and processed immediately.
  • Any level >100 μmol/L in an infant is concerning.
• In general, IEMs are defects in protein, fat, or carbohydrate metabolism or of the mitochondrial respiratory chain that result in either toxic accumulations of metabolites and/or deficiencies of substrates necessary for energy production.
• Maintaining a high degree of clinical suspicion for IEMs in sick neonates is essential to provide appropriate treatment as soon as possible.
• Delay in treatments leads to irreversible brain damage or death.

RISK FACTORS

PATHOPHYSIOLOGY

• Nitrogen is an essential building block of amino acids and a major source of ammonia from protein degradation.
  • Ammonia is highly toxic, especially to the central nervous system (CNS).
  • The major mechanism for ammonia detoxification is the urea cycle, which in the liver converts ammonia to water-soluble urea. Urea is then excreted by the kidneys.
• IEMs causing hyperammonemia interfere with urea cycle function, either directly through primary enzymatic defects of the urea cycle or indirectly, as seen in aminoacidopathies, organic acidemias, fatty acid oxidation defects, and defective carbohydrate metabolism.