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.
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.
Authors: Ludmila Pawlikowska; Sandra Strautnieks; Irena Jankowska; Piotr Czubkowski; Karan Emerick; Anthony Antoniou; Catherine Wanty; Bjorn Fischler; Emmanuel Jacquemin; Sami Wali; Samra Blanchard; Inge-Merete Nielsen; Billy Bourke; Shirley McQuaid; Florence Lacaille; Jane A Byrne; Albertien M van Eerde; Kaija-Leena Kolho; Leo Klomp; Roderick Houwen; Peter Bacchetti; Steven Lobritto; Vera Hupertz; Patricia McClean; Giorgina Mieli-Vergani; Benjamin Shneider; Antal Nemeth; Etienne Sokal; Nelson B Freimer; A S Knisely; Philip Rosenthal; Peter F Whitington; Joanna Pawlowska; Richard J Thompson; Laura N Bull Journal: J Hepatol Date: 2010-04-13 Impact factor: 25.083
Authors: Lieke M van der Velden; Catharina G K Wichers; Adriana E D van Breevoort; Jonathan A Coleman; Robert S Molday; Ruud Berger; Leo W J Klomp; Stan F J van de Graaf Journal: J Biol Chem Date: 2010-10-14 Impact factor: 5.157
Authors: Daniel H Leung; Amrita Narang; Charles G Minard; Girish Hiremath; John A Goss; Ross Shepherd Journal: Liver Transpl Date: 2016-11 Impact factor: 5.799
Authors: Lee M Bass; Deepa Patil; M Sambasiva Rao; Richard M Green; Peter F Whitington Journal: BMC Gastroenterol Date: 2010-03-13 Impact factor: 3.067