Abstract
A 12-year-old female, resident of western India, presented with a history of pruritus associated with jaundice for two months. On presentation, she had icterus with mild palpable hepatomegaly. Investigations revealed direct hyperbilirubinemia and elevated transaminases, while gamma-glutamyl transferase levels were normal. Serology for anti-hepatitis A, E, B, and C were negative. Autoimmune markers such as antinuclear antibody, smooth muscle antibody, and anti-liver kidney microsomal antibody were negative. Serum IgG levels were within the normal range. A normal magnetic resonance cholangiopancreatography ruled out any ductal abnormalities. A liver biopsy was also conducted but proved to be inconclusive. Despite extensive workup, the diagnosis remained unclear. However, genetic testing through whole exome sequencing identified a novel compound heterozygous variation, a novel in exon 5 and exon 4 of the Tight-Junction Protein 2 gene, and confirmed the diagnosis of cholestatic liver disease as progressive familial intrahepatic cholestasis type 4. This case highlights the importance of genetic testing for diagnosing cholestatic liver diseases, especially when conventional tests do not provide a clear diagnosis. Whole exome sequencing revealed a novel mutation in the TJP2 gene, ultimately confirming the diagnosis of PFIC4.