Metabolic Diseases in Hyperammonemic Newborns

Basics

Description

  • Inborn errors of metabolism are inherited defects in biosynthesis, catabolism, or transport of lipids, amino acids, or carbohydrates. The first presentation of an inborn error of metabolism can be at any age, with most cases manifesting during states of metabolic catabolism and/or increased dietary intake of an offending metabolite.
  • Clinical findings can range from acute life-threatening crises to milder, nonspecific clinical episodes of malaise, emesis, lethargy, anorexia, or even acute neuropsychiatric abnormalities.
  • Some inborn errors of metabolism present with elevated levels of ammonia (>100 μM/L). Ammonia is highly neurotoxic, and elevated levels can lead to encephalopathy and death. Maintaining a high degree of clinical suspicion in sick neonates is essential.

Epidemiology

  • Incidence and prevalence vary among different types of inborn errors of metabolism. Collectively, approximately 1 in 500 newborns are affected by one of the various inborn errors of metabolism.
  • Estimated incidence of urea cycle defects is 1:18,000. Incidence of organic acidemias is 1:1,000 and of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency ranges from 1:4,900 to 1:17,000.

Risk Factors

Genetics

  • Inheritance of most inborn errors of metabolism is autosomal recessive.
  • Ornithine transcarbamylase (OTC) deficiency (the most common urea cycle defect) is X-linked.

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).
    • A major mechanism for ammonia detoxification is the urea cycle, which converts ammonia in the liver to water-soluble urea. Urea is then excreted by the kidneys.
  • Inborn errors of metabolism causing hyperammonemia interfere with urea cycle function, either directly through primary enzymatic defects of the urea cycle or indirectly caused by liver failure, decreased production, increased use, or defective transport of a urea cycle intermediate as seen in aminoacidopathies, organic acidemias, fatty acid oxidation defects, and defective carbohydrate metabolism.

Etiology

Any biochemical defect that alters the amount of ammonia or that interferes with the detoxification of ammonia

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