ABCB4 disease: Many faces of one gene deficiency.

Abstract

ATP-binding cassette (ABC) subfamily B member 4 (ABCB4), also known as multidrug resistance protein 3 (MDR3), encoded by ABCB4, is involved in biliary phospholipid secretion, protecting hepatobiliary system from deleterious detergent and lithogenic properties of the bile. ABCB4 mutations altering canalicular ABCB4 protein function and expression may have variable clinical presentation and predispose to several human liver diseases. Well-established phenotypes of ABCB4 deficit are: progressive familial intrahepatic cholestasis type 3, gallbladder disease 1 (syn. low phospholipid associated cholelithiasis syndrome), high ɣ-glutamyl transferase intrahepatic cholestasis of pregnancy, chronic cholangiopathy, and adult biliary fibrosis/cirrhosis. Moreover, ABCB4 aberrations may be involved in some cases of drug induced cholestasis, transient neonatal cholestasis, and parenteral nutrition-associated liver disease. Recently, genome-wide association studies have documented occurrence of malignant tumours, predominantly hepatobiliary malignancies, in patients with ABCB4/MDR3 deficit. The patient's age at the time of the first presentation of cholestatic disease, as well as the severity of liver disorder and response to treatment are related to the ABCB4 allelic status. Mutational analysis of ABCB4 in patients and their families should be considered in all individuals with cholestasis of unknown aetiology, regardless of age and/or time of onset of the first symptoms.

• Authors: Eva Sticova, Milan Jirsa
• Journal: Annals of hepatology (Ann Hepatol) 2020 Mar - Apr Vol. 19 Issue 2 Pg. 126-133 ISSN: 1665-2681 [Print] Mexico
• PMID: 31759867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2019 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.

Chemical References

• ATP Binding Cassette Transporter, Subfamily B
• Cholagogues and Choleretics
• Ursodeoxycholic Acid
• multidrug resistance protein 3

Topics

• ATP Binding Cassette Transporter, Subfamily B (deficiency, genetics, metabolism)
• Age of Onset
• Alleles
• Bile Duct Diseases (genetics)
• Chemical and Drug Induced Liver Injury (genetics)
• Cholagogues and Choleretics (therapeutic use)
• Cholelithiasis (genetics)
• Cholestasis (genetics)
• Cholestasis, Intrahepatic (genetics)
• Gallbladder Diseases (genetics)
• Humans
• Liver Cirrhosis, Biliary (genetics)
• Liver Diseases (etiology, genetics)
• Parenteral Nutrition (adverse effects)
• Pregnancy Complications (genetics)
• Ursodeoxycholic Acid (therapeutic use)