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Recognize the signs

Diagnostic Evaluation

Diagnostic Evaluation


The diagnosis of a urea cycle disorder is based on the evaluation of clinical, biochemical, and molecular data, including:

  1. Plasma ammonia level: The sample must be placed immediately on ice and run STAT, or false elevations can occur. Obtaining Accurate Ammonia Levels
  2. Plasma quantitative amino acid analysis can be used to help diagnose a specific urea cycle disorder. 
  3. Urinary orotic acid is measured to distinguish CPSI deficiency and NAGS deficiency from OTC deficiency. 
  4.  Molecular genetic testing.


  1. Plasma ammonia measurement is a simple yet important screening in the ED for patients with unexplained stupor or delirium. Recognizing the symptoms of the disease is often delayed and/or mistaken. Obtaining Accurate Ammonia Levels
  2. Although UCD is usually identified in early childhood, partial or mild forms may not be recognized until unmasked by an environmental trigger that can lead to catastrophic hyperammonemic crisis.
  3. Altered consciousness should always lead to blood ammonia measurement.
  4. Ornithine transcarbamylase deficiency should be suspected in adult patients who develop recurrent hyperammonemia and encephalopathy following bariatric surgery.
  5. The diagnosis of NAGS or OTC deficiency should be considered in nonhepatic adult patients with hyperammonemic coma, particularly if they have a history of protein avoidance and neurological symptoms.


 Treatment options for Urea Cycle Disorders

 New England Consortium of Metabolic Programs Treatment Guidelines

 Rare Diseases Clinical Research Network Urea Cycle Disorders Consortium


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