Vol. 7, Issue 1, Part A (2025)

Background: Progressive Familial Intrahepatic Cholestasis (PFIC) comprises a group of rare autosomal recessive liver disorders characterized by impaired bile flow, leading to chronic cholestasis. PFIC type 7 (PFIC7), associated with mutations in the USP53 gene, is an exceptionally rare subtype with limited reports in the literature.
Case Presentation: We present the case of an 18-year-old male with a three-year history of recurrent jaundice and generalized pruritus. He reported 4-5 self-resolving episodes, each lasting several months, with no prior medical evaluation. Clinical examination revealed icterus and excoriations, without signs of liver failure. Laboratory evaluation demonstrated marked conjugated hyperbilirubinemia, elevated alkaline phosphatase, and mild transaminitis. Viral, autoimmune, and metabolic liver disease panels were negative. Imaging, including MRCP and CT abdomen, was unremarkable. Liver biopsy revealed intracytoplasmic cholestasis with minimal portal fibrosis and inflammatory infiltration. Given the recurrent cholestasis and inconclusive conventional workup, Whole Exome Sequencing (WES) was pursued. WES identified a homozygous pathogenic splice site variant in USP53 (c.822+1del), consistent with a diagnosis of PFIC7. 
Management and Outcome: The patient was initiated on ursodeoxycholic acid and reported symptomatic improvement within two weeks. Genetic counselling was provided for familial risk assessment.
Conclusion: This case underscores the importance of considering rare genetic aetiologies such as PFIC7 in adolescents with unexplained recurrent cholestatic jaundice. Early genomic diagnosis facilitates tailored management, prognostication, and family counselling, particularly in populations with a high rate of consanguinity.