Excerpt from Dubin-Johnson Syndrome

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Background

First described in 1954, Dubin-Johnson syndrome (DJS) is an autosomal recessive disease characterized by conjugated hyperbilirubinemia and deposition of melaninlike pigment in hepatocytes. Although urinary excretion of coproporphyrin I is increased, liver function remains normal. Long-term follow-up is indicated for neonatal DJS because of possible recurrence and second attacks of jaundice in later life. Disruption of functionally important ATP–binding cassette (ABC) domains in multidrug resistant protein 2 (MRP2) may be related to earlier onset of the disease.

Onset occurs most often in early adulthood; onset during infancy is rare. DJS is caused by mutations of the ABC transporter encoding gene (MRP2/cMOAT/ABCC2), which is mapped to band 10q24. Recently, the genomic DNA sequence of a Caucasian female patient with DJS was analyzed using DNA sequencing. The analysis identified a homozygous missense mutation, C2302T (Materna, 2003). This DJS-causing alteration results in the amino acid exchange Arg768Trp.

Pathophysiology

The conjugated hyperbilirubinemia observed in DJS results from a defect in the transfer of endogenous and exogenous anionic conjugates from hepatocytes into the bile. Lysosomal storage of pigment causes the liver to turn black. A hallmark of DJS is the unusual ratio between the byproducts of heme biosynthesis, urinary coproporphyrin I and coproporphyrin III. In unaffected individuals, the ratio of coproporphyrin III to coproporphyrin I is approximately 3-4:1. This ratio is inverted in patients with DJS.

The molecular basis for DJS is related to defects in the multispecific anion transporter (cMOAT) gene, which belongs to the ABC transporter superfamily. Identified mutations rest in the cytoplasmic domain where binding occurs; thus, disruption of this region probably results in a loss of function.

Frequency

United States

Overall prevalence of DJS is extremely low.

International

DJS occurs in 1 case per 1300 persons of Iranian Jewish descent, primarily because of inbreeding.

Mortality/Morbidity

For the most part, patients are asymptomatic and have normal life spans. Jaundice is the most consistent finding in patients with DJS. Some neonates present with cholestasis.

Race

In persons of Iranian Jewish descent, prevalence is increased to 1 case per 1300 people, primarily because of inbreeding.

Sex

DJS occurs in both sexes but has a tendency to predominate in males. In women with DJS, pregnancy or oral contraceptive use can cause overt jaundice.

Age

DJS is rarely detected before puberty, although neonatal cases have been reported. Onset during infancy is rare; onset occurs most often in early adulthood.

Please click here to view the full topic text: Dubin-Johnson Syndrome