LAUSR

Abstract Objectives Citrin deficiency (CD) is an autosomal recessive disease caused by mutations of the SLC25A13 gene, plasma bile acid profiles detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS) could be an efficient approach for early diagnosis of intrahepatic cholestasis. The aim of this study was to investigate the genetic testing and clinical characteristics of a series of patients with CD, and to analyse plasma bile acid profiles in CD patients. Methods We retrospectively analysed data from 14 patients (12 males and 2 females, age 1–18 months, mean 3.6 months) with CD between 2015 and 2021, including demographics, biochemical parameters, genetic test results, treatment, and clinical outcomes. In addition, 30 cases (15 males and 15 females, age 1–20 months, mean 3.8 months) with idiopathic cholestasis (IC) served as a control group. Plasma 15 bile acid profiles were compared between the CD and IC groups. Results Eight different mutations of the SLC25A13 gene were detected in the 14 patients diagnosed with CD, of which three novel variants of the SLC25A13 gene were investigated, the c.1043C>T (p.P348L) in exon11, the c.1216dupG (p.A406 Gfs*13) in exon12 and the c.135G>C (p.L45F) in exon3. More than half of the patients with CD had prolonged neonatal jaundice, which was associated with significantly higher alpha-fetoprotein (AFP) levels, hyperlactatemia and hypoglycemia. The majority of patients were ultimately self-limited. Only one patient developed liver failure and died at the age of 1 year due to abnormal coagulation function. In addition, the levels of glycochenodeoxycholic acid (GCDCA), taurocholate (TCA), and taurochenodeoxycholic acid (TCDCA) were significantly increased in the CD group compared with those in the IC group. Conclusions Three novel variants of the SLC25A13 gene were identified for the first time, providing a reliable molecular reference and expanding the SLC25A13 gene spectrum in patients with CD. Plasma bile acid profiles could be a potential biomarker for non-invasive early diagnosis of patients with intrahepatic cholestasis caused by CD.