A Rare Cause of Portal Hypertension: ZFYVE19 Gene Mutation

Abstract

Mutations in the ZFYVE19 gene represent a rare cause of progressive familial intrahepatic cholestasis (PFIC), specifically PFIC type 9 (PFIC9). PFIC9 is an autosomal recessive disorder typically beginning in early childhood and characterized by elevated gamma-glutamyl transferase (GGT) levels. We report a 6-year-old boy who presented with portal hypertension, splenomegaly, and elevated liver enzymes. Whole-exome sequencing (WES) confirmed a homozygous pathogenic variant in ZFYVE19, establishing a diagnosis of PFIC9. Treatment with ursodeoxycholic acid (UDCA) resulted in improved liver enzyme levels without additional complications. The ZFYVE19 mutation has recently been identified as a cause of PFIC9 and may represent an overlooked etiology in idiopathic neonatal hepatitis. WES significantly improves diagnostic accuracy in children with unexplained cholestasis and should be more widely utilized.