Dubin-Johnson syndrome and intrahepatic cholestasis of pregnancy in a Sri Lankan family: a case report

• Published in: BMC research notes Vol. 10; no. 1; p. 487
• Main Authors: Kularatnam, Grace Angeline Malarnangai, Warawitage, Dilanthi, Vidanapathirana, Dinesha Maduri, Jayasena, Subashini, Jasinge, Eresha, de Silva, Nalika, Liyanarachchi, Kirinda Liyana Arachchige Manoj Sanjeeva, Wickramasinghe, Pujitha, Devgun, Manjit Singh, Barbu, Veronique, Lascols, Olivier
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.09.2017; BioMed Central; BMC
• Subjects: Base Sequence; Bile; Bile acids; Bilirubin; Biopsy; Blood; Care and treatment; Case Report; Case reports; Case studies; Causes of; Child, Preschool; Cholestasis; Cholestasis, Intrahepatic - complications; Cholestasis, Intrahepatic - genetics; Complications and side effects; Conjugated hyperbilirubinemia; Coproporphyrin isomers; Diagnosis; Dubin-Johnson syndrome; Exons - genetics; Family; Female; Gallbladder diseases; Genes; Genetics; Hepatitis; Hepatocytes; Hepatocytes - pathology; Humans; Hyperbilirubinemia; Intrahepatic cholestasis of pregnancy; Isomers; Jaundice; Jaundice, Chronic Idiopathic - complications; Jaundice, Chronic Idiopathic - genetics; Jaundice, Obstructive; Life Sciences; Liver - pathology; Liver diseases; Liver pigmentation; Multidrug resistance; Multidrug resistant organisms; Mutation; Parenchyma; Pigments; Polymerase chain reaction; Pregnancy; Pregnancy Complications - genetics; Proteins; Pruritus; Sequence Analysis, DNA; Sri Lanka; Studies; Urine; France; Sri Lanka; Intrahepatic cholestasis of pregnancy; Case report; ABCC2; Bile acids; Liver pigmentation; Coproporphyrin isomers; ABCB11; Conjugated hyperbilirubinemia; Dubin–Johnson syndrome
• ISSN: 1756-0500; 1756-0500
• DOI: 10.1186/s13104-017-2811-6

Dubin-Johnson syndrome and intrahepatic cholestasis of pregnancy are rare chronic liver disorders. Dubin-Johnson syndrome may manifest as conjugated hyperbilirubinemia, darkly pigmented liver, presence of abnormal pigment in the parenchyma of hepatocytes and abnormal distribution of the coproporphyrin isomers I and III in the urine. Intrahepatic cholestatic jaundice of pregnancy presents as pruritus, abnormal liver biochemistry and increased serum bile acids. A Sri Lankan girl presented with recurrent episodes of jaundice. She had conjugated hyperbilirubinaemia with diffuse, coarse brown pigments in the hepatocytes. Urine coproporphyrin examination suggested Dubin-Johnson syndrome. Genetic studies confirmed missense homozygous variant p.Trp709Arg in the ATP-binding cassette sub-family C member 2 gene ABCC2 that encodes the Multidrug resistance-associated protein 2 that causes Dubin-Johnson syndrome. The gene study of the mother revealed the same missense variant in ABCC2/MRP2 but with a heterozygous status, and in addition a homozygous missense variant p.Val444Ala in the ATP-binding cassette, sub-family B member 11 gene ABCB11 that encodes the bile salt export pump. Dubin-Johnson syndrome should be considered when the common causes for conjugated hyperbilirubinaemia have been excluded, and patient has an increased percentage of direct bilirubin relative to total bilirubin concentration. Its early diagnosis prevents repeated hospital admissions and investigations. Knowledge of a well known homozygous variant in ABCB11 gene could help in the management of pregnancy.