Genetics of Hyperammonemia Clinical Presentation

Updated: Sep 20, 2018
  • Author: Karl S Roth, MD; Chief Editor: Maria Descartes, MD  more...
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The multiple primary causes of hyperammonemia, specifically those due to urea cycle enzyme deficiencies, vary in presentation, diagnostic features, and treatment. For these reasons, the members of the family of urea cycle defects are not individually considered in this article. However, the common denominator, hyperammonemia, can be clinically manifested by some or all of the following: anorexia, irritability, heavy or rapid breathing, lethargy, vomiting, disorientation, somnolence, asterixis (rarely), combativeness, obtundation, coma, cerebral edema, and death, if treatment is not forthcoming or effective. As a consequence, the most striking clinical findings of each individual urea cycle disorder relate to this constellation and roughly temporal sequence of events.

The most helpful diagnostic information of history in a patient with suspected genetic hyperammonemia is intercurrent illnesses with exaggerated lethargy and vomiting.




Poor growth may be evident.

Hypothermia is occasionally seen.

Head, ears, eyes, nose, and throat (HEENT)

Papilledema may be present if cerebral edema and increased intracranial pressure have ensued.


Tachypnea or hyperpnea may be present.

Apnea and respiratory failure may occur in latter stages.


Hepatomegaly is usually mild, if present.


Neurologic history may include the following:

  • Poor coordination

  • Dysdiadochokinesia

  • Hypotonia or hypertonia

  • Ataxia

  • Tremor

  • Seizures

  • Lethargy that progresses to combativeness to obtundation to coma

  • Decorticate or decerebrate posturing



Urea cycle defects with resulting hyperammonemia are due to deficiencies of the enzymes involved in the metabolism of waste nitrogen. The enzyme deficiencies lead to disorders with nearly identical clinical presentations. The exception is arginase, the last enzyme of the cycle. Arginase deficiency causes a somewhat different set of signs and symptoms.

Genetic defects of the urea cycle include the following: