Citrin Deficiency

  • Yuan-Zong Song
  • Masahide Yazaki
  • Takeyori Saheki


Citrin deficiency arises from biallelic mutations in SLC25A13 gene, and can manifest in newborns or infants as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), in older children as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and in adults as adult-onset citrullinemia type II (CTLN2). The diagnosis of citrin deficiency is based on characteristic biochemical findings and identification of biallelic pathogenic variants in SLC25A13 gene. Lactose-free and medium-chain triglycerides (MCT)-enriched formula and fat-soluble vitamins yield satisfactory outcomes in most NICCD cases. For FTTDCD, besides dietary treatment, sodium pyruvate may improve growth. For CTLN2, liver transplantation is effective, but arginine, sodium pyruvate, and MCT oil may delay the need for liver transplantation.


CTLN2 (adult-onset type II citrullinemia) NICCD (neonatal intrahepatic cholestasis caused by citrin deficiency) FTTDCD (failure to thrive and dyslipidemia caused by citrin deficiency) Aspartate-glutamate carrier Malate-aspartate shuttle 







 ATP-binding cassette


ATP-binding cassette, subfamily G, member 5/8






Aspartate-glutamate carrier


Alkaline phosphatase


Alanine aminotransferase


Argininosuccinate synthetase


Aspartate aminotransferase


Bile salt export pump




Argininosuccinate synthetase deficiency or classical citrullinemia


Adult-onset type II citrullinemia


Failure to thrive and dyslipidemia caused by citrin deficiency


Gas chromatography-mass spectrometry




Medium-chain fatty acid


Medium-chain triglyceride


Multidrug-resistant protein 3


Tandem mass spectrometry


Neonatal intrahepatic cholestasis caused by citrin deficiency


Open reading frame


Total bile acids


Total bilirubin/direct bilirubin


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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Yuan-Zong Song
    • 1
  • Masahide Yazaki
    • 2
    • 3
  • Takeyori Saheki
    • 4
  1. 1.Department of Pediatrics, The First Affiliated HospitalJinan UniversityGuangzhouChina
  2. 2.Institute for Biomedical SciencesShinshu UniversityMatsumotoJapan
  3. 3.Department of Clinical Laboratory MedicinesShinshu University School of Health SciencesMatsumotoJapan
  4. 4.Department of Hygiene and Health Promotion MedicineKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan

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