Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency: Clinical Features, Genetic Characteristics, and Treatment Outcomes
Background: Mutations in human SLC25A13 gene cause citrin deficiency, can result in severe neonatal cholestasis and adverse long-term outcomes. This study aims to investigate the clinical manifestations, genetic characteristics, and outcomes of Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD). Methods: A total of 15 children with genetic diagnosis of NICCD were analyzed in this retrospective study, and 15 infants with Idiopathic neonatal cholestasis (INC) as control group. The clinical symptoms and laboratory findings were compared between the groups, and the genetic mutations associated with NICCD were investigated. All the children were followed up to 2 months later after treatment. Results: Of these participants, the age was from 1 to 6 months (mean, 2.63 months). Both groups presented with typical cholestatic hepatitis such as jaundice, hyperbilirubinemia and abnormal liver function. There was a significantly elevated level of bile acids, cholesterol, low-density lipoprotein cholesterol, lactate, blood ammonia, prothrombin time, International Normalized Ratio, Alpha-fetoprotein, methionine, citrulline, and threonine, while a lower level of total protein in NICCD infants compared to the INC group. Twenty-five distinct mutations were identified in children with NICCD. The most prevalent gene mutation was c.852_855del (52%), followed by mutation c.762T>A (20%) which was not reported previously. A treatment regimen of medium-chain triglyceride (MCT) and lactose-restricted formula was given, and all NICCD infants demonstrated improved bilirubin, AST levels, along with an increase in total protein and albumin after two months. Conclusion: NICCD infants predominantly present with intrahepatic cholestasis, bile acids, prolonged jaundice, lactic acidosis, hyperammonemia, coagulopathy, hyper-AFP, and citrullinemia. The most common mutation was c.852_855del in this study, followed by c.762T>A. The prognosis of two-month treatment with the combination of MCT diet and lactose-restricted therapy was good.