Benign recurrent intrahepatic cholestasis associated with mutations of the bile salt export pump.
A young patient with recurrent attacks of intrahepatic cholestasis is described. On the basis of clinical presentation, laboratory findings and genetic analysis, the diagnosis of benign recurrent intrahepatic cholestasis type 2 (BRIC-2) was established. By the use of BSEP-specific antibodies, almost complete absence of BSEP from the canalicular membrane of liver cells was detected in the patient. Two different BSEP mutations were found. One mutation (E186G) had been described in one BRIC-2 case; the second mutation (V444A) is more frequent and has been linked to intrahepatic cholestasis of pregnancy. It is concluded that this form of compound heterozygosity of the BSEP gene reduces the amount of BSEP protein due to protein instability or mis-targeting, which is the underlying reason for reduced bile salt excretion and cholemia.
Kubitz
Ralf
R
Department of Gastroenterology, Hepatology and Infectiology, Heinrich-Heine University, Düsseldorf, Germany. kubitz@med.uni-duesseldorf.de
Keitel
Verena
V
Scheuring
Sybille
S
Köhrer
Karl
K
Häussinger
Dieter
D
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D000293:Adolescent; D001647:Bile Acids and Salts / Q000378:metabolism*; D001706:Biopsy; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D006801:Humans; D016623:Ion Pumps / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction
C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001647:Bile Acids and Salts; D016623:Ion Pumps