Progressive familial intrahepatic cholestasis - farnesoid X receptor deficiency due to mutation: A case report.

Background: Functioning farnesoid X receptor (FXR; encoded by ) is key to normal bile acid homeostasis. Biallelic mutations in are reported in a few children with intrahepatic cholestasis. We describe a boy with progressive familial intrahepatic cholestasis and homozygous mutation in .

Case Summary: A boy had severe neonatal cholestasis with moderate hypercholanemia and persistently elevated alpha-fetoprotein. Despite medical treatment, coagulopathy was uncontrollable, prompting liver transplantation at age 8 mo with incidental splenectomy. The patient experienced catch-up growth with good liver function and did not develop allograft steatosis. However, 1 year after transplant, he died from an acute infection, considered secondary to immunosuppression and asplenia. A homozygous protein-truncating mutation, c.547C > T, p.(Arg183Ter), was subsequently identified in , and both parents were shown to be heterozygous carriers. Absence of FXR and of bile salt export pump expression was confirmed by immunostaining of explanted liver.

Conclusion: Severe cholestasis with persistently high alpha-fetoprotein and modest elevation of serum bile acid levels may suggest FXR deficiency. Some patients with FXR deficiency may not develop allograft steatosis and may respond well to liver transplantation.