TY - JOUR
T1 - Progressive familial intrahepatic cholestasis type 1 and extrahepatic features
T2 - No catch-up of stature growth, exacerbation of diarrhea, and appearance of liver steatosis after liver transplantation
AU - Lykavieris, Panayotis
AU - Van Mil, Saskia
AU - Cresteil, Danièle
AU - Fabre, Monique
AU - Hadchouel, Michelle
AU - Klomp, Leo
AU - Bernard, Olivier
AU - Jacquemin, Emmanuel
PY - 2003/9/1
Y1 - 2003/9/1
N2 - Background/Aims: Progressive familial intrahepatic cholestasis characterized by normal serum gamma-glutamyltransferase activity can be due to mutations in familial intrahepatic cholestasis type 1 (FIC1) (ATP8B1), a gene expressed in several organs. In some cases, it is associated with extrahepatic features. We searched for FIC1 mutations and analyzed the outcome of extrahepatic features after liver transplantation in two children with this form of progressive familial intrahepatic cholestasis associated with chronic unexplained diarrhea and short stature. Methods: FIC1 sequence was determined after polymerase chain reaction (PCR) of genomic lymphocyte DNA and/or reverse transcription-PCR of liver or lymphocyte RNA. Results: A homozygous amino acid change deletion was found in one child. The second child harboured compound heterozygous missense and nonsense mutations. In both children, despite successful liver transplantation, evolution (follow-up: 9.5-11 years) was characterized by exacerbation of diarrhea and no catch-up of stature growth, and appearance of liver steatosis. Conclusions: Progressive familial intrahepatic cholestasis characterized by normal serum gamma-glutamyltransferase activity and extrahepatic features corresponds to progressive familial intrahepatic cholestasis type 1. Extrahepatic symptomatology is not corrected or may be aggravated by liver transplantation, impairing life quality.
AB - Background/Aims: Progressive familial intrahepatic cholestasis characterized by normal serum gamma-glutamyltransferase activity can be due to mutations in familial intrahepatic cholestasis type 1 (FIC1) (ATP8B1), a gene expressed in several organs. In some cases, it is associated with extrahepatic features. We searched for FIC1 mutations and analyzed the outcome of extrahepatic features after liver transplantation in two children with this form of progressive familial intrahepatic cholestasis associated with chronic unexplained diarrhea and short stature. Methods: FIC1 sequence was determined after polymerase chain reaction (PCR) of genomic lymphocyte DNA and/or reverse transcription-PCR of liver or lymphocyte RNA. Results: A homozygous amino acid change deletion was found in one child. The second child harboured compound heterozygous missense and nonsense mutations. In both children, despite successful liver transplantation, evolution (follow-up: 9.5-11 years) was characterized by exacerbation of diarrhea and no catch-up of stature growth, and appearance of liver steatosis. Conclusions: Progressive familial intrahepatic cholestasis characterized by normal serum gamma-glutamyltransferase activity and extrahepatic features corresponds to progressive familial intrahepatic cholestasis type 1. Extrahepatic symptomatology is not corrected or may be aggravated by liver transplantation, impairing life quality.
KW - Children
KW - Extrahepatic features
KW - Familial intrahepatic cholestasis type 1
KW - Liver transplantation
KW - Progressive familial intrahepatic cholestasis
UR - http://www.scopus.com/inward/record.url?scp=0042830239&partnerID=8YFLogxK
U2 - 10.1016/S0168-8278(03)00286-1
DO - 10.1016/S0168-8278(03)00286-1
M3 - Article
C2 - 12927934
AN - SCOPUS:0042830239
SN - 0168-8278
VL - 39
SP - 447
EP - 452
JO - Journal of Hepatology
JF - Journal of Hepatology
IS - 3
ER -