Dubin-Johnson syndrome

The Dubin-Johnson syndrome (DJS) is an inherited liver disease, clinically characterized by chronic predominantly conjugated hyperbilirubinemia, and histopathologically by deposition of brownish-black pigment in hepatocytes.

The prevalence in the general population is unknown. The DJS affects individuals of all ethnic backgrounds but is most common in Iranian and Moroccan Jews in which, due to founder mutations has been described as occurring in up to 1/1, 300 individuals.

Patients present during adolescence or young adulthood recurrent jaundice without mild to moderate itching, often triggered by intercurrent illness, pregnancy, contraception or drugs. Abdominal pain and fatigue are sometimes observed during outbreaks, hepatosplenomegaly may be present in rare cases. The serum total bilirubin (mainly in conjugated form: the ratio of serum bilirubin conjugate total is 50-80%) is high, usually between 2 and 5 mg / dl (rarely up to 20 mg / dl). The activities of hepatic enzymes (ie aminotransferase, alkaline phosphatase and gamma glutamyl transpeptidase), the total concentration of bile acids, the levels of albumin and prothrombin time are normal. An association was observed with a deficiency of coagulation factor VII (see this term), especially in Iranian and Moroccan Jews. Histological studies reveal a granular pigment deposition typical brownish-black in the cytosol of hepatocytes, mainly in the centrilobular area, no other histological abnormalities.

Transmission and Treatment

The DJS is transmitted in an autosomal recessive manner and is caused by homozygous mutations in the ABCC2 gene. The gene encodes a transporter ABCC2 the apical membrane, ATP-dependent, which controls the outflow of bilirubin glucuronides and other organic anions connecting the hepatocyte into the bile.

The diagnosis should be suspected in patients who exhibit conjugated hyperbilirubinemia alone (ie no change in the activities of liver enzymes) in the absence of any septic condition, abnormal liver ultrasound or medication potentially interfering. In this context, the characteristic pattern of urinary excretion of coproporphyrin (ie a high proportion of coproporphyrin I (above 80%) with a normal level of coproporphyrin total) is usually diagnostic for DJS. Biliary scintigraphy with 99mTc-HIDA, showing delayed or non-visualization of the gallbladder and bile ducts of the liver and prolonged viewing can also be useful. The definitive diagnosis can be obtained by molecular analysis of gene ABCC2. Despite the histological studies permit a definitive diagnosis, liver biopsy is not systematically performed considering the invasive nature of the procedure along with a benign prognosis of the disease.

The main differential diagnosis is otherwise mostly conjugated hyperbilirubinemia, Rotor syndrome (RT; see this term).

There is no curative treatment for DJS, although the administration of phenobarbital in the short term have been described as reducing serum levels of bilirubin in some cases.

The DJS is a benign disease and the prognosis is good for patients, emphasizing the need for a correct diagnosis to avoid diagnostic procedures, treatment and follow-up unnecessary. It is observed progression to liver failure, hepatic fibrosis or cirrhosis.