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[Increased citrulline]

Citrullinemia (CIT)


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 the ASA synthetase and lyase, respectively, in the urea cycle result in hyperammonemia and elevated citrulline. 


  • Contact family to inform them of the newborn screening result and ascertain clinical status (poor feeding, vomiting, lethargy, tachypnea)
  • Immediate consult with metabolic specialist
  • Evaluate infant (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 state newborn screening program (Carleigh Soule at 307-777-6297) 

Confirmation of Diagnosis: 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 may be increased in both disorders which can be determined by urine organic acid analysis. In citrin deficiency blood lactate and pyruvate will be elevated. 

Clinical Considerations: Citrullinemia and Argininosuccinic Acidemia can present acutely in the newborn period with hyperammonia, 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 development and to prevent hyperammonemia. 

Additional Information: (Click on the name to take you to the website) 

Genetic Home Reference                                         Wyoming Department of Health                                     

Gene Tests – Gene Clinics                                        Colorado Newborn Screening                                   

American Academy of Pediatrics


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