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Newborn Screening ACT Sheet

[Increased Arginine]
Amino Aciduria/Urea Cycle Disorder

Differential Diagnosis: Citrullinemia I, argininosuccinic acidemia, citrullinemia II (citrin deficiency), pyruvate carboxylase deficiency.

Condition Description: The urea cycle is the enzyme cycle whereby ammonia is converted to urea. In citrullinemia and in argininosuccinic acidemia, defects in argininosuccinic acid (ASA) synthetase and lyase, respectively, in the urea cycle result in hyperammonemia and elevated citrulline

Citrullinemia I, argininosuccinic acidemia, citrullinemia II (citrin deficiency), pyruvate carboxylase deficiency.


  • Contact family to inform them of the newborn screening result and ascertain clinical status (poor feeding, vomiting, lethargy, tachypnea).
  • Immediate consult with pediatric metabolic specialist.
  • Evaluate the newborn (poor feeding, vomiting, lethargy, hypotonia, tachypnea, seizures, and signs of liver disease). Measure blood ammonia. If any sign is present or infant is ill initiate emergency treatment for hyperammonemia in consultation with metabolic specialist.
  • Transport to hospital for further treatment in consultation with metabolic specialist.
  • Initiate timely confirmatory/diagnostic testing and management, as recommended by specialist.
  • Provide family with basic information about hyperammonemia.
  • Report findings to newborn screening program.

Diagnostic Evaluation:

Plasma ammonia to determine presence of hyperammonemia. In citrullinemia, plasma amino acid analysis will show increased citrulline whereas in argininosuccinic acidemia, argininosuccinic acid will also be present. Orotic acid, which may be detected by urine organic analysis, may be increased in both disorders. Note: “Urine organic analysis” may not identify orotic acid in some laboratories because of the tests employed. In citrin deficiency, liver enzymes, lactic acid and bilirubin may be elevated. Blood lactate and pyruvate will be elevated in pyruvate carboxylase deficiency.

Clinical Considerations:

Citrullinemia and argininosuccinic acidemia can present acutely in the newborn period with hyperammonemia, seizures, failure to thrive, lethargy, and coma. Later signs include mental retardation. Citrin deficiency may present with cholestatic liver disease in the newborn period. Pyruvate carboxylase deficiency produces coma seizures and life-threatening ketoacidosis. Treatment for ASA and citrullinemia is to promote normal growth and developmental and to prevent hyperammonemia.

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