Multidrug-resistant P-glycoprotein 3 (MDR3) is a phospholipid translocator 
encoded by the ABCB4 gene located on chromosome 7. MDR3 mediates the 
translocation of phosphatidylcholine across the canalicular membrane of the 
hepatocyte into bile. Severe MDR3 deficiency typically occurs during childhood 
with progressive cholestasis evolving to cirrhosis and liver failure, requiring 
liver transplantation. In this article, we report 2 pediatric cases of severe 
MDR3 deficiency with paucity of interlobular bile ducts. Both underwent living 
donor liver transplantation at our center for decompensated liver disease and 
portal hypertension. We diagnosed severe MDR3 deficiency in both the cases with 
negative MDR3 immunostaining in the explanted liver. Genetic studies revealed 
homozygous deletion single base pair deletion in exon 24 of the ABCB4 gene in 
the second child. The patients are on regular follow-up after liver transplant 
and are doing well. Our report highlights that cholangiopathy in MDR3 deficiency 
can lead to ductopenia in pediatric livers.