A novel homozygous NR1H4 mutation in idiopathic elevated transaminases

We describe a patient with a homozygous loss-of-function mutation in NR1H4, presenting with idiopathic mild elevation of transaminases. His presentation differs from the limited previously reported cases of progressive familial intrahepatic cholestasis type 5 (PFIC5). Case report: A 7-year-old boy was admitted to our outpatient clinic due to persistently elevated transaminases since 12 months of age. While PFIC5 is typically a rapidly progressive disease requiring liver transplantation, this patient’s laboratory results showed normal gamma-glutamyl transferase (GGT), international normalized ratio (INR), albumin, and alpha-fetoprotein (AFP) levels. Liver biopsy revealed only mild fibrosis. Over a two-year follow-up, he has remained stable with mild transaminase elevation. Conclusion: Infants with cryptogenic liver disease should be evaluated for NR1H4 mutations-associated PFIC5. This mutation may represent a novel metabolic etiology of idiopathic, mildly elevated transaminases.