Urea Cycle disorders

Key Features

• Typical presentation is infantile encephalopathy; later onset presentations are common with cyclic vomiting or encephalopathy with illness or protein load

• Diagnosis is suspected with the finding of hyperammonemia frequently with minimal other laboratory findings

Clinical Findings

• Patients with severe defects usually present in infancy with severe hyperammonemia, vomiting, and encephalopathy, which is rapidly fatal

• Patients with milder genetic defects may present with vomiting, encephalopathy, or liver failure after increased protein ingestion or infection

Diagnosis

• Blood ammonia should be measured in any acutely ill newborn in whom a cause is not obvious

• Early hyperammonemia is associated with hyperventilation and respiratory alkalosis

• Prenatal diagnosis is most commonly done by molecular methods

Treatment

• During treatment of acute hyperammonemic crisis, protein intake should be stopped, and glucose and lipids should be given to reduce endogenous protein breakdown from catabolism

• Long-term treatment includes

  • Low-protein diet

  • Oral administration of arginine or citrulline

  • Sodium benzoate or sodium phenylbutyrate (a prodrug of sodium phenylacetate)

• Hemodialysis or hemofiltration is indicated for severe or persistent hyperammonemia

• Liver transplantation

  • May be curative

  • Indicated for patients with severe disorders