Prenatal Diagnosis of Progressive Familial Intrahepatic Cholestasis Type 2

Szu-Ta Chen; Huey-Ling Chen; Yi-Ning Su; Yu-Jung Liu; Yen-Hsuan Ni; Hong-Yuan Hsu; Chia-Shiang Chu; Nai-Yu Wang; Mei-Hwei Chang


J Gastroenterol Hepatol. 2008;23(9):1390-1393. 

In This Article

Abstract and Introduction


Background and Aim:Progressive familial intrahepatic cholestasis type 2 (PFIC2) results from genetic defects of the hepatobiliary bile salt export pump (BSEP, ABCB11) at chromosome 2q24. Patients with progressive cholestasis and liver cirrhosis usually need liver transplantation in the first decade. Mutations in ABCB11 are also associated with benign recurrent intrahepatic cholestasis type 2 and intrahepatic cholestasis of pregnancy in adult patients. We aimed to make the prenatal diagnosis of PFIC2.
Methods:Genetic diagnosis was performed by genomic DNA analysis. Prenatal genetic diagnosis was made by fetal amniotic DNA and chorionic DNA analysis.
Results:We report on two families of PFIC2 with inherited compound heterozygous mutations of ABCB11 (M183V and R303K in Family 1, V284L and 1145delC in Family 2) from the parents. An infant with heterozygous M183V mutation was later born healthy in Family 1. A fetus with compound heterozygous missense mutation V284L and 1145delC was terminated in Family 2.
Conclusion:Prenatal diagnosis of PFIC2 was helpful to prevent further affected children in families with this fatal disease.


Progressive familial intrahepatic cholestasis (PFIC) is characterized by early onset of persistent cholestasis, neonatal hepatitis, progressive biliary cirrhosis, and hepatic failure in the first or second decade. Significant pruritus, hepatomegaly, and failure to thrive are typical features of this disease. The disease was first described as Byler's disease, also known as PFIC type 1 caused by mutations in ATP8B1 in Amish kindreds in 1965.[1,2] Furthermore, other isolated populations with typical PFIC findings in the Middle East have been identified as PFIC type 2 (PFIC2), and heterozygosity mapping resulted in a gene locus on chromosome 2q24,[3] whereas the third type PFIC with high gamma-glutamyltransferase (GGT) has been shown to be caused by mutations in ABCB4, encoding multidrug resistance protein 3 (MDR3).[4] Patients with PFIC2 have more severe symptoms rapidly progressing into cirrhosis which are present at an earlier age.[5]

PFIC2 is caused by mutations of the ABCB11 gene encoding the bile salt export pump (BSEP) which is an ATP-binding cassette transmembrane transporter located on the bile canalicular membrane. The mutations could affect BSEP function by either interfering with the biogenesis or trafficking of the protein correctly into the canalicular membrane or by impairing the substrates binding to BSEP to diminish the transport function.[6] Bile secretion failure results in intracellular bile salts accumulation which is highly cytotoxic and leads to the development of cholangiopathies. In adults, mutations in ABCB11 may result in benign recurrent intrahepatic cholestasis type 2 (BRIC2), in comparison with the BRIC type 1 causing by ATP8B1 mutations.[7] Even without history of cholestasis in childhood, adult patients with BSEP mutations could also be predisposed towards intrahepatic cholestasis in pregnancy.[8]

We report two families in which the parents each carried one ABCB11 mutation. According to the different results of prenatal analysis of fetal ABCB11 gene mutation, the parents made the decision to keep a pregnancy in Family 1 and to terminate the fetus in Family 2.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: