Citrin deficiency presents in a number of syndromes, one of which affects neonates and infants. This is termed Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency (NICCD).


Chromosome location: 7q21.3

Gene affected: SLC25A13

Protein: calcium-binding mitochondrial carrier protein Aralar2

Function: liver-type aspartate-glutamate carrier isoform 2 (AGC2)

Deficiency affects aerobic glycolysis, gluconeogenesis, urea cycle, protein synthesis, nucleotide synthesis


Inheritance: autosomal recessive


Clinical features:

(1) age < 1 year

(2) transient neonatal intrahepatic cholestasis

(3) hepatomegaly with diffuse fatty liver (steatosis)

(4) failure to thrive and growth retardation

(5) positive response to a diet low in carbohydrate (with high protein, high triglyceride, etc)


Laboratory findings:

(1) hypoproteinemia

(2) coagulopathy due to decrease in coagulation factors

(3) hemolytic anemia

(4) variable hypoglycemia

(5) elevated plasma amino acids: citrulline, methionine, threonine



(1) cirrhosis

(2) acute liver failure

(3) severe infection(s)

(4) life-threatening bleeding


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