Characteristics of patients with neonatal intrahepatic cholestasis caused by citrin deficiency in China: long-term follow-up outcomes

OBJECTIVE: Citrin deficiency (CD) is an autosomal recessive disease caused by mutations in the SLC25A13 gene. This study aimed to expand the current body of data on Chinese patients with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) by analyzing their clinical characteristics, genetic mutation spectrum, and long-term follow-up outcomes. METHODS: From May 2013 to April 2025, 60 children diagnosed with NICCD were enrolled in this retrospective study. Related data were obtained from medical records. RESULTS: Among 60 patients, common presentations included elevated aspartate aminotransferase (100%), infantile cholestasis (95.0%), elevated citrulline (96.7%), hyperlactatemia (93.3%), hypoproteinemia (81.7%), coagulation dysfunction (60.0%), hyperammonemia (48.3%) and chubbier face (36.7%). Twenty-eight SLC25A13 variants were detected, with c.852_855delTATG (42.7%), IVS16ins3kb (15.4%) and c.615+5G>A (10.3%) being the most frequent. All patients were fed with lactose-free milk powder enriched with medium-chain triglycerides (MCT) after diagnosis or suspected diagnosis. Ten patients were lost to follow-up. Among 50 followed patients, 30 were followed for > 5 gt; 5 years. Twenty-four patients showed typical dietary features. After discharge, 11 had hypoglycemic episodes, 5 had growth retardation, 11 had dyslipidemia and 3 progressed to failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD). All patients remained in stable condition. CONCLUSION: Patients with neonatal intrahepatic cholestasis caused by citrin deficiency present with a variety of clinical manifestations. c.852_855delTATG, IVS16ins3kb and c.615+5G>A are the mutation hotspots of the SLC25A13 gene in Zhejiang, China. Early intervention leads to a good prognosis.