Background and objective: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is rare disease. It is a novel metabolism disease which caused by deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier encoded by the SLC25A13 gene. Citrin deficiency causes NICCD and adult-onset type II citrullinemia (CTLN2) with severe hepatic-neurology syndrome. The study presents some clinical features, laboratory finding, results molecular analysis and following process of 96 NICCD.
Methods: Prospective description study.
Results: Two hundred and thirty-six patients, who had hepatic troubles and were diagnosed SLC25A13 mutations by PCR/PCR-RFLP enrolled in this study. There were 96 in 236 patients were diagnosed NICCD by molecular analysis. Some NICCD clinical manifestations include: Jaundice (95.8%), hepatomegaly (31.3%), steatorrhea (89.6%), chubby face (88.5%), splenomegaly (29.4%), and faint (2.1%). Laboratory finding: Hyperbilirubinemia (95.8%), increase AST (100%), ALT (88.5%), AST/ALT ratio >2.5 (89.6%), coagulation disorder (87.5%), hypoproteinemia (82.3%), hypoalbuminemia (84.4%), hyperammonemia (92.7%), 100% patients had elevation of AFP and 70.8% had increase of citrullin. DNA analysis of SLC25A13 revealed combinations of 851del4, 1638ins23, IVS6 + 5G > A and IVS16ins3kb with 5 genotypes, 89 homozygous and 7 compound heterozygous. No relation between phenotype and genotype has been found. With supportive treatment and nutritional manipulation most of patients in group recovered completely by the age 18 months. However, there were eight patients had died of uncompensative hepatic failure.
Conclusions: NICCD should be considered in the differential diagnosis of cholestatic and hepatic failure infants. Phenotype of NICCD is very polymorphic and not always benign. All NICCD should be long term followed up.
