NR1H4-related Progressive Familial Intrahepatic Cholestasis 5: Further Evidence for Rapidly Progressive Liver Failure.

Pathogenic sequence variants in the nuclear bile acid receptor FXR, encoded by NR1H4, have been reported in a small number of children with low-GGT cholestasis progressing to liver failure. We describe three additional children from two unrelated families with cholestasis and liver failure due to pathologic variants in NR1H4. One patient underwent liver transplantation and has had good clinical outcomes in six years of follow-up. While that patient has biochemical evidence of increased bile acid synthetic activity, he has not experienced post-transplant diarrhea or allograft steatosis, as has been reported among other transplanted patients.