Clinical variability of mutations in the ABCB11 gene: a case report.

Progressive familial intrahepatic cholestasis (PFIC) includes a group of infrequent genetic diseases with autosomal recessive heredity, characterized by intrahepatic cholestasis, usually in childhood and in adolescence. It is caused by defective bile salt secretion and other bile components. The progression leading to liver failure and cirrhosis usually appears in the first few decades of life. There are three types of PFIC (Table I). PFIC 1, previously called Byler disease, was discovered first, and it is caused by mutations in the ATP8B1 gene (FIC-1); therefore, it is currently called FIC1 deficiency. PFIC 2, previously called Byler syndrome, is due to mutations in the ABCB11 gene, which encodes a protein that works as a canalicular bile salt transporter. Therefore, PFIC 2 is also called BSEP (bile salt export pump) deficiency. Finally, PFIC 3, whose origin resides in the ABCB4 gene, is also called MDR3 (class III multidrug resistance p-glycoprotein) deficiency. Benign recurrent intrahepatic cholestasis (BRIC) is also a group of diseases related to disorders of the secretion and transportation of bile salt. It differs from PFIC because of its indolent progression, which does not end in cirrhosis. Two types of BRIC have been described, based on the associated genetic defect: BRIC 1 (ATP8B1) and BRIC 2 (ABCB11).