A Novel Compound Heterozygous Mutation in ABCB4 Gene Leading to Cholelithiasis, Progressive Familial Intrahepatic Cholestasis (Type 3), and Cirrhosis in a Child

Smita Malhotra,Anupam Sibal,Nida Mirza

doi:10.1055/s-0040-1717106

Abstract

AbstractProgressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive disorders of childhood which presents with intermittent or progressive episodes of cholestasis, with jaundice and pruritus as most common presenting symptoms. PFIC type 3 occurs due to mutations in the ABCB4 gene, mutation in this gene has wide spectrum of features which include intrahepatic stones, cholelithiasis, PFIC type 3, and intrahepatic cholestasis of pregnancy. Here, we are reporting a peculiar case of young male adolescent with novel variant compound heterozygote missense mutation in ABCB4 gene who had gall stone as initial symptom, followed by symptoms of PFIC and eventually decompensated chronic liver disease.

Highlights

Case ReportProgressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders which presents with intermittent or progressive episodes of cholestasis, clinically most common presenting symptoms are jaundice and pruritus
ABCB4 mutation have been associated with several biliary disorders which include transient neonatal cholestasis, low phospholipid-associated cholelithiasis syndrome, intrahepatic cholestasis of pregnancy, drug-induced liver injury, adult biliary fibrosis, or cirrhosis and intrahepatic cholangiocarcinoma.[2,3]
Later heterozygous mutations in the ABCB4 gene in adult patients were found associated with intrahepatic sludge, gallbladder cholesterol gallstones, and intrahepatic cholestasis of pregnancy, it is considered that female sex hormones may reduce the expression of the normal allele during pregnancy resulting in clinical cholestasis in the heterozygous.[5,6]

Summary

Introduction

Progressive familial intrahepatic cholestasis (PFIC) is a group of autosomal recessive disorders which presents with intermittent or progressive episodes of cholestasis, clinically most common presenting symptoms are jaundice and pruritus. A 14-year-old previously asymptomatic male presented with complains of progressive jaundice associated with moderate-to-severe pruritus since 1 month He was apparently alright till the age of 9 years when he had acute onset of jaundice and abdominal pain; investigations revealed multiple gall stones for which cholecystectomy was performed at that time and he improved symptomatically. He remained asymptomatic for 5 years except with mild intermittent episodes of pruritus, in this duration, he was growing well and had no episodes of jaundice, bleeding from any site, abdominal distension, or altered sensorium. His family was counselled regarding the need for liver transplantation in future

Discussion

Conclusion