Progressive familial intrahepatic cholestasis type 5 due to a novel mutation in the NR1H4 gene

Progressive familial intrahepatic cholestasis type 5 is a rare cause of neonatal cholestasis with low-to-normal levels of gamma-glutamyl transpeptidase. It is caused by mutations in the NR1H4 gene, which encodes farnesoid X receptor, an important transcription factor for bile formation. It also plays an essential role in biliary acid homeostasis. It is known to have a severe course with a rapid progression to end-stage liver failure. Very few cases have been reported worldwide. The authors report the case of a 2-month-old female infant presenting with prolonged jaundice due to progressive familial intrahepatic cholestasis type 5. The laboratory assessment showed a normal level of gamma-glutamyl transpeptidase and an elevated rate of serum bilirubin, transaminase activity, bile acids, and alpha-fetoprotein. Whole-exome sequencing identified a novel homozygous pathologic variant in the NR1H4 gene, described for the first time. At the age of 6 months, the patient died because of liver failure and disseminated intravascular coagulation. In conclusion, this is the first Tunisian case report of PFIC type 5; the diagnosis was made based on a molecular study. The off-label use of ursodeoxycholic acid was ineffective.