Adult progressive intrahepatic cholestasis associated with genetic variations in ATP8B1 and ABCB11.
Severe intrahepatic cholestasis with low serum gamma-glutamyltranspeptidase (gamma-GT) activity is exceptionally rare in adult patients, and its association with multi-genetic alterations of bile salt transporters has not been reported. We investigated a 25-year-old man presenting with a four-year history of jaundice. Laboratory and radiographic examinations revealed clinical pictures of progressive intrahepatic cholestasis with low gamma-GT. Serial liver histopathology demonstrated cirrhosis resulting from progressive persistent cholestatic injury. Genetic sequencing studies for the entire coding exons of ATP8B1 and ABCB11 uncovered a heterozygous missense mutation 1798 C->T (R600W) in ATP8B1, and a homozygous nucleotide substitution 1331 T->C (V444A) in ABCB11. In conclusion, this is a rare case of adult onset progressive intrahepatic cholestasis with low gamma-GT associated with heterozygous ATP8B1 mutation and homozygous ABCB11 polymorphism. Further studies are necessary to investigate the impact of heterozygous R600W mutation and whether other cholestatic disorders are multi-genetic.
Hsu
Yao-Chun
YC
Division of Gastroenterology, Department of Internal Medicine, Lo-Tung Pohai Hospital, I-Lan.
Chen
Huey-Ling
HL
Wu
Mu-Zon
MZ
Liu
Yu-Jung
YJ
Lee
Po-Huang
PH
Sheu
Jin-Chuan
JC
Chen
Chien-Hung
CH