Citrin deficiency

The two phenotypes of citrin deficiency are citrullinemia type II (CTLN2) and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). CTLN2 typically presents in adulthood with recurring neuropsychiatric symptoms associated with episodic hyperammonemia, including disorientation, irritability, delusions, delirium, seizures, and coma that can lead to death from brain edema. Onset is sudden usually between the ages of 20-50 and often prompted by medication, alcohol or surgery. The symptoms of NICCD are milder and present in children under one year of age as transient intrahepatic cholestasis, hypoproteinemia, growth retardation, hypoglycemia, fatty liver, mild liver dysfunction, and/or high levels of plasma alpha-fetoprotein. A few NICCD patients have a severe form of the disorder with liver damage associated with tyrosinemia and require liver transplantation. Most NICCD patients’ symptoms disappear by one year of age; however, some NICCD patients later develop CTLN2 with neuropsychiatric symptoms several decades later. Patients with both CTLN2 and NICCD tend to have a preference for protein-rich and lipid-rich foods and avoid sugar-rich and carbohydrate-rich foods. Some individuals with NICCD later develop severe CTLN2. The male to female ratio in CTLN2 is 2.4 to 1, while the ratio in NICCD is roughly equal. Citrin deficiency was once thought to be restricted to Japan where the carrier rate is 1 in 65. However, affected individuals in other countries have now been identified. The carrier rate is also high in the East Asian population: China (1 in 65), Taiwan (1 in 48) and Korea (1 in 112).

Tests Available

Forms and Documents

Test Details

  • Confirmation of biochemical diagnosis
  • Confirmation of clinical diagnosis
  • Carrier testing
  • Prenatal diagnosis in at risk pregnancies
  • Capillary Sequencing Reflex to Exon Array


4-5 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs


  • 796.6 Abnormal findings on neonatal screening
  • 277.8 Other specified disorders of metabolism
* For price inquiries please email


  1. Yasuda et al., (2000) Hum Genet 107:537-545.
  2. Lu et al., (2005) J Hum Genet 50:338-346.
  3. Tabata et al., (2008) J Hum Genet 53:534-545.
  4. Kobayashi et al., (1999) Nat Genet 22:159-163.
  5. Ko et al., (2007) Int J Mol Med 20:809-815.
  6. Yamaguchi et al., (2002) Hum Mutat 19:122-130.
  7. Kobayashi, K. (Updated [July 2, 2008]) Citrin Deficiency In: GeneReviews at Genetests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at