Hepatic steatosis and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in Taiwanese infants

OBJECTIVES: To explore the prevalence of hepatic steatosis and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in Taiwanese infants with idiopathic intrahepatic cholestasis. STUDY DESIGN: The liver specimens from 69 infants with idiopathic intrahepatic cholestasis were reviewed (1993-2004); 11 of them (14.7%) had hepatic steatosis. Six patients with hepatic steatosis participated in the genetic study for the SLC25A13 gene under parental consent. RESULTS: Infants with cholestasis and hepatic steatosis had lower aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels than those with cholestasis alone. Three of the six infants in the genetic study had homozygous 851del4 mutation; for the others, homozygous 1638ins23 mutation, compound heterozygous 851del4/IVS6+5G-->A mutation, and heterozygous IVS6+5G-->A mutation were found for each one. Eleven of the total 12 alleles (91.7%) were demonstrated to have SLC25A13 gene mutations. CONCLUSIONS: Metabolic and genetic studies for NICCD should be performed in Asian infants with idiopathic intrahepatic cholestasis and hepatic steatosis. The 851del4 mutation on the SLC25A13 gene accounts for the major genotype expression of patients with NICCD in Taiwan.