How to Identify Dubin-Johnson Syndrome

Typically, most pediatric gastroenterologists want to remember that the gross appearance of the liver in patients with Dubin-Johnson is black as this is rumored to be a frequently asked question for board testing.  Practically, though other features are important to recognize since the color of the liver is not readily evident except during surgery.  As such, a recent retrospective study (T Togawa et al. J Pediatr 2018; 196: 161-7) describes 10 neonatal patients from Japan.

Key findings:

  • Only 3 of the 8 patients who underwent liver biopsy had a grossly black liver
  • All liver specimens showed no expression of multidrug resistance-associated protein 2 and increased expression of the bile salt export pump protein
  • Homozygous or compound heterozygous pathogenic variants of ABCC2/MRP2 (ATP-binding cassette subfamily C member 2/multidrug resistance-associated protein 2) were identified in all patients

The clinical course was similar in the patients:

  • Cholestasis self-limited/benign: “severe cholestasis developed in the neonatal period…reaching a maximum at 19 to 60 days. Cholestasis then decreased and disappeared at 2 to 9 months of age.”  Acholic stools were common during the cholestatic phase.
  • Serum AST and ALT remained consistently normal
  • There was no hepatosplenomegaly and no failure to thrive

My take: Dubin-Johnson syndrome is much easier to identify with the availability of genetic panels.

Related blog post: Dubin-Johnson Syndrome

 

Dubin-Johnson Syndrome

From NEJM:

A 48-year-old woman scheduled to receive a laparoscopic cholecystectomy underwent a preoperative evaluation that disclosed conjugated hyperbilirubinemia…

A biopsy specimen revealed coarse, deep-brown, pigmented granules on periodic acid–Schiff staining (Panel B), primarily at the canalicular pole of the hepatocytes and especially in the pericentral zones, with otherwise well-preserved lobular architecture. Expression of the multidrug-resistance–associated protein 2 (MRP2) was absent on anti–MRP2 immunohistochemical analysis (Panel C; see also comparison with control specimen [inset]). A diagnosis of the Dubin–Johnson syndrome was confirmed. This syndrome is an autosomal recessive disorder that is caused by a mutation in MRP2 that results in deficient canalicular expression of MRP2 and impaired secretion of conjugated bilirubin into the bile. Such mutations cause an isolated increase in serum levels of conjugated bilirubin and the appearance of a black liver, without associated sequelae.

Dubin-Johnson