NR1H4‐related Progressive Familial Intrahepatic Cholestasis 5

ABSTRACT Pathogenic sequence variants in the nuclear bile acid receptor FXR, encoded by NR1H4, have been reported in a small number of children with low‐γ‐glutamyl transferase (GGT) cholestasis progressing to liver failure. We describe 3 additional children from 2 unrelated families with cholestasis and liver failure because of pathologic variants in NR1H4. One patient underwent liver transplantation and has had good clinical outcomes in 6 years of follow‐up. Although 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.