[Recurrent intrahepatic cholestasis of pregnancy and chain-like choledocholithiasis in a female patient with stop codon in the ABDC4-gene of the hepatobiliary phospholipid transporter].
We report the case of a 40-years-old female patient with recurrent cholestatic liver disease who presented twice with severe intrahepatic cholestasis of pregnancy and pronounced choledocholithiasis between pregnancies. Bile duct stones were removed endoscopically and a laparoscopic cholecystectomy was performed after the second pregnancy. Liver histology revealed intrahepatic cholestasis with portal inflammation and fibrosis, resembling progressive familial intrahepatic cholestasis (PFIC). Molecular genetic studies identified the heterozygous mutation c.957C > T in the ABCB4 gene encoding the hepatobiliary phospholipid transporter. This is the first report of this mutation that introduces a stop codon in an index patient with intrahepatic cholestasis of pregnancy and multiple bile duct stones. In addition, we detected the ABCB11 polymorphism V 444A, which is associated with a decreased expression of the bile salt export pump. Whereas homozygous carriers of the ABCB4 mutation develop PFIC type 3, the heterozygous ABC transporter mutations represent genetic risk factors for cholelithiasis and recurrent cholestatic hepatitis upon challenge with oral contraceptives or during pregnancy. Of note, the patient presented with normal serum gamma-glutamyltranspeptidase activities during pregnancy-associated cholestatic episodes but normal liver enzymes after delivery, whereas choledocholithiasis was associated with high gamma-glutamyl transpeptidase levels. It is unknown whether ursodeoxycholic acid prevents cholestasis or gallstones in patients with ABCB4 deficiency.
Muehlenberg
K
K
Medizinische Klinik II, Krankenhaus Barmherzige Brüder, Regensburg. klaus.muehlenberg@barmherzige-regensburg.de
Wiedmann
K
K
Keppeler
H
H
Sauerbruch
T
T
Lammert
F
F
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D002760:Cholangiopancreatography, Endoscopic Retrograde; D017081:Cholecystectomy, Laparoscopic; D042883:Choledocholithiasis / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics / Q000601:surgery; D002780:Cholestasis, Intrahepatic / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation; D010743:Phospholipids / Q000235:genetics; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011248:Pregnancy Complications / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics; D012008:Recurrence
C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D010743:Phospholipids