Progressive familial intrahepatic cholestasis type 1 and extrahepatic features: no catch-up of stature growth, exacerbation of diarrhea, and appearance of liver steatosis after liver transplantation.
OBJECTIVE
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.
Lykavieris
Panayotis
P
Department of Pediatrics, Hepatology Unit, Bicêtre University Hospital, Assistance Publique--Hôpitaux de Paris, 78, rue du Général Leclerc, 94275 Le Kremlin Bicêtre, France.
van Mil
Saskia
S
Cresteil
Danièle
D
Fabre
Monique
M
Hadchouel
Michelle
M
Klomp
Leo
L
Bernard
Olivier
O
Jacquemin
Emmanuel
E
D000251:Adenosine Triphosphatases / Q000235:genetics*; D000595:Amino Acid Sequence; D001827:Body Height; D002780:Cholestasis, Intrahepatic / Q000150:complications* / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery; D018389:Codon, Nonsense; D003967:Diarrhea / Q000209:etiology / Q000503:physiopathology*; D018450:Disease Progression; D005234:Fatty Liver / Q000209:etiology*; D017353:Gene Deletion; D006128:Growth; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007223:Infant; D016031:Liver Transplantation / Q000009:adverse effects*; D008297:Male; D009154:Mutation; D020125:Mutation, Missense
D018389:Codon, Nonsense; D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human