Progressive familial intrahepatic cholestasis type 2 with trisomy x reverse Occam’s razor: a case report

Abstract

Progressive familial intrahepatic cholestasis type 2 (PFIC-2) is a rare autosomal recessive liver disorder caused by ABCB11 mutations, leading to severe cholestasis and liver failure. Triple X syndrome (47,XXX) is a sex chromosome aneuploidy with variable clinical features. An 80-day-old female presented with severe neonatal cholestasis and conjugated hyperbilirubinemia. Genetic testing confirmed biallelic ABCB11 variants consistent with PFIC-2 and a supernumerary X chromosome (47,XXX). Despite supportive therapy, she developed intractable ascites and died of septicemia. This case highlights the importance of genomic testing in neonatal cholestasis and the need for multidisciplinary care in complex dual genetic diagnoses.