Dubin-Johnson Syndrome

Alternative Names

  • DJS
  • Hyperbilirubinemia II
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Metabolic disorders

OMIM Number

237500

Mode of Inheritance

Autosomal recessive

Gene Map Locus

10q24

Description

Dubin Johnson Syndrome (DJS) is a rare autosomal recessive genetic disorder, which is characterized by an increase of conjugated bilirubin without elevation of liver enzymes. This conjugated hyperbilirubinemia is the result of defects in the transfer of anionic conjugates from hepatocytes into the bile. Bilirubin is conjugated, but not secreted into the bile, leading to a cellular accumulation and eventful reflux of the conjugated bilirubin into the circulation.

Patients with DJS are mostly asymptomatic. The major symptom of the condition is mild jaundice, which although may appear only at puberty or adulthood and may remain throughout life. The jaundice may be aggravated by pregnancy, alcohol, or oral contraceptives. In addition, the accumulation of melanin-like pigment in the liver in DJS tends to provide a dark brown appearance to the organ. Another hallmark of the condition is an increase in the corpoporphyrin I:corpoporphyrin III ratio. In addition, a majority of the patients have been found to have reduced prothrombin activity, due to lower levels of Factor VII.

Diagnosis of the condition makes use of measurements of serum bilirubin and urinary corpoporphyrin levels. Liver biopsy may also be required. Since DJS is a benign condition, treatment is usually not required. Life expectancy is normal.

Molecular Genetics

DJS results from mutations in the human Canalicular Multispecific Organic Anion Transporter (cMOAT), an ATP binding cassette superfamily member, which plays a role in mediating active hepetobiliary excretion of numerous organic anions. Mutations in the gene have been found to result in impaired transport of the non-bile salt anions across the canalicular membrane of the hepatocytes, resulting in the conjugated hyperbilirubinemia and accumulation of the hepatocellular pigment, characteristic of DJS. Mutations in the functionally critical ATP binding region of the protein are especially important.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
237500.1Saudi ArabiaFemale Conjugated hyperbilirubinemia; Hyperthyr...NM_000392.5:c.2273G>THomozygousAutosomal, RecessiveMonies et al. 2017

Other Reports

Bahrain

Al-Mahroos et al. (1996) reported the case of a one-month-old boy, born to consanguineous parents with full term gestation and normal vaginal delivery, who presented with pale and greasy stool and dark yellowish urine. The patient's family had a history of sickle cell disease and G6PD deficiency. Two of his adult relatives had had a history of recurrent jaundice since childhood. Physical examination revealed a normal, though jaundiced infant. Liver function tests, however, showed abnormal values of total bilirubin (221 mmol/L), direct bilirubin (221 mmol/L), alkaline phosphatase (707 IU/L), alanine aminotransferase (90 IU/L), gamma glutamyl transferase (245 IU/L). Stool cultures showed no pathogens. However, the stool fat was found to be high. FAB-MS showed elevation of certain bile acids and alcohols, suggesting impaired liver function. A large liver with dense texture was visible in the hepatobiliary ultrasound. Liver biopsy performed at six weeks and later ten weeks of age showed a normal lobular architechture, normal bile ductules, and occasional giant cell transformation. However, prominent centrilobular brown pigmentation was found in the liver, which was positive for PAS and Mason Fontana stain and diastase resistant. The patient was diagnosed with DJS, and treated with phenobarbitol, hydrolysed formula, and vitamins A, D, E, and K. Al-Mahroos et al. (1996) suggested that the cholestasis noticed in the patient could be due to an effect secondary to the accumulation of non-bile acid organic anions. At two years of age, he was asymptomatic, with only intermittent episodes of mild jaundice.

[Al-Mahroos F, Satir AA, Al-Awadhi MA, Al-Yousif R. Dubin-Johnson syndrome and neonatal cholestasis: Case report and review of pathogenesis. Bahrain Med Bull. 1996; 18(1):23-5.]

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