Dubin-Johnson syndrome - Symptoms, Causes, Images, and Treatment Options

Diseases

Highlights & Basics

Key Highlights

Dubin-Johnson syndrome is an autosomal recessive condition characterized by jaundice. Total bilirubin levels usually range between 2 and 5 mg/dL, with increased plasma conjugated bilirubin.
A dark pigment accumulates in the liver, giving it a characteristic black color.
Primary defect is a mutation in an apical canalicular membrane protein responsible for excretion of bilirubin.
Jaundice is worsened by an intercurrent illness, pregnancy, and oral contraceptives.
A unique pattern of urinary excretion of coproporphyrins (by-products of heme synthesis) aids in the diagnosis.

Masson-Fontana stain showing the pigment in a patient with DJS

Personal collection of Professor Bernard Portmann, King's College Hospital, London, with permission

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Definition

Epidemiology

Etiology

Pathophysiology

Images

Masson-Fontana stain showing the pigment in a patient with DJS
Immunohistochemistry for canalicular multispecific organic anion transporter in patient showing the pigment, but no canalicular structures
Immunohistochemistry for canalicular multispecific organic anion transporter in a control, showing no pigment, but irregularly branching canalicular structures can be seen

Citations

Key Articles

Dubin IN, Johnson FB. Chronic idiopathic jaundice with unidentified pigment in the liver cells: a new clinicopathologic entity with report of 12 cases. Medicine. 1954 Sep;33(3):155-97.[Abstract]
Dubin IN. Chronic idiopathic jaundice: a review of 50 cases. Am J Med. 1958 Feb;24(2):268-92.[Abstract]
Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017 Jan;112(1):18-35.[Abstract]
Machida I, Wakusawa S, Sanae F, et al. Mutational analysis of the MRP2 gene and long-term follow-up of Dubin-Johnson syndrome in Japan. J Gastroenterol. 2005 Apr;40(4):366-70.[Abstract]

Referenced Articles

1. Dubin IN, Johnson FB. Chronic idiopathic jaundice with unidentified pigment in the liver cells: a new clinicopathologic entity with report of 12 cases. Medicine. 1954 Sep;33(3):155-97.[Abstract]
2. Sprinz H, Nelson RS. Persistent nonhemolytic hyperbilirubinemia associated with lipochrome-like pigment in liver cells: report of 4 cases. Ann Intern Med. 1954 Nov;41(5):952-62.[Abstract]
3. Dubin IN. Chronic idiopathic jaundice: a review of 50 cases. Am J Med. 1958 Feb;24(2):268-92.[Abstract]
4. Javitt NB, Kondo T, Kuchiba K. Bile acid secretion in Dubin-Johnson syndrome. Gastroenterology. 1978 Nov;75(5):931-2.[Abstract]
5. Rastogi A, Krishnani N, Pandey R. Dubin-Johnson syndrome: a clinicopathologic study of twenty cases. Indian J Pathol Microbiol. 2006 Oct;49(4):500-4.[Abstract]
6. Junge N, Goldschmidt I, Wiegandt J, et al. Dubin-Johnson Syndrome as differential diagnosis for neonatal cholestasis. J Pediatr Gastroenterol Nutr. 2021 May 1;72(5):e105-11.[Abstract][Full Text]
7. Seligsohn U, Shani M. The Dubin-Johnson syndrome and pregnancy. Acta Hepatogastroenterol. 1977 Jun;24(3):167-9.[Abstract]
8. Di Zoglio JD, Cardillo E. The Dubin-Johnson syndrome and pregnancy. Obstet Gynecol. 1973 Oct;42(4):560-3.[Abstract]
9. Skornick YG, Klausner JM, Lelcuk S, et al. Cholelithiasis in Dubin-Johnson syndrome. Surg Gynecol Obstet. 1983 Nov;157(5):447-9.[Abstract]
10. Sotelo-Avila C, Danis RK, Krafcik J, et al. Cholecystitis in a 17-year-old boy with recurrent jaundice since childhood. J Pediatr. 1988 Apr;112(4):668-74.[Abstract]
11. Kondo T, Yagi R. Dubin-Johnson syndrome in a neonate. N Engl J Med. 1975 May 8;292(19):1028-9.[Abstract]
12. Nakata F, Oyanagi K, Fujiwara M, et al. Dubin-Johnson syndrome in a neonate. Eur J Paediatr. 1979;132(4):299-301.[Abstract]
13. Haimi-Cohen Y, Merlob P, Marcus-Eidlits T, et al. Dubin-Johnson syndrome as a cause of neonatal jaundice: the importance of coproporphyrins investigation. Clin Pediatr (Phil). 1998 Aug;37(8):511-3.[Abstract]
14. Tsai WH, Teng RJ, Chu JS, et al. Neonatal Dubin-Johnson syndrome. J Paediatr Gastroenterol Nutr. 1994 Feb;18(2):253-4.[Abstract]
15. Shani M, Seligsohn V, Gilon E, et al. Dubin-Johnson syndrome in Israel: clinical, laboratory and genetic aspects of 101 cases. Q J Med. 1970 Oct;39(156):549-67.[Abstract]
16. Zlotogora J. Hereditary disorders among Iranian Jews. Am J Med Genet. 1995 Jul 31;58(1):32-7.[Abstract]
17. Mor-Cohen R, Zivelin A, Fromovich-Amit Y, et al. Age estimates of ancestral mutations causing factor VII deficiency and Dubin-Johnson syndrome in Iranian and Moroccan Jews are consistent with ancient Jewish migrations. Blood Coagul Fibrinolysis. 2007 Mar;18(2):139-44.[Abstract]
18. Paulusma CC, Kool M, Bosma PJ, et al. A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome. Hepatology. 1997 Jun;25(6):1539-42.[Abstract][Full Text]
19. Toh S, Wada M, Uchiumi T, et al. Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/CMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome. Am J Hum Genet. 1999 Mar;64(3):739-46.[Abstract][Full Text]
20. Van Kuijck MA, Kool M, Merkx GF, et al. Assignment of the canalicular multispecific organic anion transporter gene (CMOAT) to human chromosome 10q24 and mouse chromosome 19d2 by fluorescent in situ hybridization. Cytogenet Cell Genet. 1997;77(3-4):285-7.[Abstract]
21. Mor-Cohen R, Zivelin A, Rosenberg N, et al. A novel ancestral splicing mutation in the multidrug resistance protein 2 gene causes Dubin-Johnson syndrome in Ashkenazi Jewish patients. Hepatology Res. 2005 Feb;31(2):104-11.[Abstract]
22. Kartenbeck J, Leuschner U, Mayer R, et al. Absence of the canalicular isoform of the MRP gene-encoded conjugate export pump from the hepatocytes in Dubin-Johnson syndrome. Hepatology. 1996 May;23(5):1061-6.[Abstract]
23. Jedlitschky G, Hoffmann U, Kroemer HK. Structure and function of the MRP2 (ABCC2) protein and its role in drug disposition. Expert Opin Drug Metab Toxicol. 2006 Jun;2(3):351-66.[Abstract]
24. Varma RR, Grainger JM, Scheuer PJ. A case of Dubin-Johnson syndrome complicated by acute hepatitis. Gut. 1970 Oct;11(10):817-21.[Abstract]
25. Hunter FM, Sparks RD, Flinner RI. Hepatitis with resulting mobilization of hepatic pigment in a patient with Dubin-Johnson syndrome. Gastroenterology. 1964 Dec;47:631-5.[Abstract]
26. Ware AJ, Eigenbrodtt EH, Naftalis J, et al. Dubin Johnson syndrome and viral hepatitis. Gastroenterology. 1974 Sep;67(3):560-1.[Abstract]
27. Ware AJ, Eigenbrodtt EH, Shorey J. Viral hepatitis complicating the Dubin-Johnson syndrome. Gastroenterology. 1972 Aug;63(2):331-9.[Abstract]
28. Erlinger S, Arias IM, Dhumeaux D. Inherited disorders of bilirubin transport and conjugation: new insights into molecular mechanisms and consequences. Gastroenterology. 2014 Jun;146(7):1625-38.[Abstract][Full Text]
29. Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017 Jan;112(1):18-35.[Abstract]
30. Bar-Meir S, Baron J, Seligson U, et al. 99mTc-HIDA cholescintigraphy rotor in Dubin-Johnson syndromes. Radiology. 1982 Mar;142(3):743-6.[Abstract]
31. Al-Hussaini A, AlSaleem B, AlHomaidani H, et al. Clinical, biochemical, and molecular characterization of neonatal-onset Dubin-Johnson syndrome in a large case series from the Arabs. Front Pediatr. 2021 Nov;9:741835.[Abstract][Full Text]
32. Talaga ZJ, Vaidya PN. Dubin Johnson syndrome. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2022. [Abstract][Full Text]
33. The familial conjugated hyperbilirubinemias. Semin Liver Dis. 1994 Nov;14(4):386-94.[Abstract]
34. Frank M, Doss M, de Carvalho DG. Diagnostic and pathogenetic implications of urinary coproporphyrin excretion in Dubin-Johnson syndrome. Hepatogastroenterology. 1990 Feb;37(1):147-51.[Abstract]
35. Rocchi E, Balli F, Gibertini P, et al. Coproporphyrin excretion in healthy newborn babies. J Pediatr Gastroenterol Nutr. 1984 Jun;3(3):402-7.[Abstract]
36. Lyu Y, Wei X, Xu J, et al. [Diagnosis of a patient with Dubin-Johnson syndrome by using next generation sequencing]. [in chi]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2019 Mar 10;36(3):242-245.
37. Wu L, Zhang W, Jia S, et al. Mutation analysis of the ABCC2 gene in Chinese patients with Dubin-Johnson syndrome. Exp Ther Med. 2018 Sep 3;16(5):4201-4206.[Abstract][Full Text]
38. Mayatepek E, Lehmann WD. Defective hepatobilary leukotriene elimination in patients with Dubin-Johnson syndrome. Clin Chim Acta. 1996 May 30;249(1-2):37-46.[Abstract]
39. Togawa T, Mizuochi T, Sugiura T, et al. Clinical, pathologic, and genetic features of neonatal Dubin-Johnson Syndrome: a multicenter study in Japan. J Pediatr. 2018 May;196:161-167.e1.[Abstract]
40. Lee JH, Chen HL, Chen HL, et al. Neonatal Dubin-Johnson syndrome: long-term follow-up and MRP2 mutations study. Pediatr Res. 2006 Apr;59(4 pt 1):584-9.[Abstract][Full Text]
41. Summerfield JA, Scott J, Berman M, et al. Benign recurrent intrahepatic cholestasis: studies of bilirubin kinetics, bile acids, and cholangiography. Gut. 1980 Feb;21(2):154-60.[Abstract]
42. Wareham NJ, Dickson CJ, Baskerville PA. Benign recurrent intrahepatic cholestasis. J R Soc Med. 1985 Nov;78(11):955-6.[Abstract][Full Text]
43. American College of Radiology. ACR appropriateness criteria®: abnormal liver function tests. 2023 [internet publication].[Full Text]
44. Machida I, Wakusawa S, Sanae F, et al. Mutational analysis of the MRP2 gene and long-term follow-up of Dubin-Johnson syndrome in Japan. J Gastroenterol. 2005 Apr;40(4):366-70.[Abstract]
45. Lindberg MC. Hepatobiliary complications of oral contraceptives. J Gen Intern Med. 1992 Mar-Apr;7(2):199-209.[Abstract]
46. Cohen L, Lewis C, Arias IM. Pregnancy, oral contraceptives and chronic familial jaundice with predominantly conjugated hyperbilirubinemia (Dubin-Johnson syndrome). Gastroenterology. 1972 Jun;62(6):1182-90.[Abstract]