A female case of progressive familial intrahepatic cholestasis type 3 caused by heterozygous mutations of ABCB4 gene and her cirrhosis improved after treatment of ursodeoxycholic acid

Background: Progressive familial intrahepatic cholestasis (PFIC) is a group of rapidly progressing autosomal recessive genetic diseases characterized by intrahepatic cholestasis. PFIC-3 is caused by mutations in the ATP binding cassette subfamily B member 4 gene (ABCB4) encoding multidrug-resistant protein 3 (MDR3/ABCB4) protein which can lead to the absence of phosphatidylcholine, cholangiopathy, bile duct loss and biliary cirrhosis. Patients usually present in infancy or childhood, but cirrhosis and portal hypertension may be the first manifestation in older children or young people. Case presentation: A 25-year-old young woman with recurrent abnormal hepatic function was mainly characterized by increased gamma glutamyl transpeptisae (GGT) and bile acid with cryptogenic cirrhosis. After 7 months of treatment with ursodeoxycholic acid (UDCA), Her hepatic pathology suggested there were also obvious widening and venous fibrosis around the portal vein, and slight bile duct hyperplasia at the edge of the portal area. Infiltration of inflammatory cells around the portal vein and hepatocyte ABCB4/MDR3 protein was basically normal. Sequencing indicated the patient had heterozygous mutations in the ABCB4 gene: c.2696C>G and wes[hg19]7q21.12(87032513-87033422)×1. Through SWISS-MODEL Predict for protein structures, the missense mutation results in protein side chain missing a methyl group (-CH3), and the deletion mutation results in the serious damage to the structure of MDR3 protein. Through the analysis of pathogenicity prediction software, the mutations led to PFIC3. After treatment of UDCA for 29 months, her cirrhosis was improved, hepatic function was close to normal. Conclusion The novel heterozygous mutation is the molecular pathological cause of PFIC3 in this patient. Young patients with cryptogenic cirrhosis should all undergo work up for ABCB4. Diagnosis of PFIC3 early and continuous treatment of UDCA are the key to improve the prognosis and delay the occurrence of end-stage liver disease.