Rotor-type hyperbilirubinaemia has no defect in the canalicular bilirubin export pump.

Abstract

BACKGROUND:

The cause of Rotor syndrome (RS), a rare-familial conjugated hyperbilirubinaemia with normal liver histology, is unclear. We hypothesized that RS can be an allelic variant of Dubin-Johnson syndrome, caused by mutation in ABCC2, and investigated ABCC2 (gene) and ABCC2 (protein) in two patients with RS.

METHODS:

A 57-year-old male presented with a 5-year history of predominantly conjugated hyperbilirubinaemia (170 micromol/l). Urinary porphyrin excretion was increased; cholescintigraphy revealed no chromoexcretion. A 68-year-old male presented with lifelong conjugated hyperbilirubinaemia (85 micromol/l). Bromosulfophthalein elimination was typical for RS. Both patients had histologically normal liver, without pigment. ABCC2 expression was investigated by confocal fluorescence microscopy. ABCC2 was sequenced from genomic DNA and cDNA, and exon deletions/duplications were sought by comparative genomic hybridization on a custom micro-array.

RESULTS:

In both patients, ABCC2 was expressed unremarkably at the apical membrane of hepatocytes and no sequence alterations were found in 32 exons, adjacent intronic regions and the promoter region of ABCC2.

CONCLUSIONS:

Rotor-type hyperbilirubinaemia is not an allelic variant of ABCC2 deficiency.

• Authors: Martin Hrebícek, Tomás Jirásek, Hana Hartmannová, Lenka Nosková, Viktor Stránecký, Robert Ivánek, Stanislav Kmoch, Dita Cebecauerová, Libor Vítek, Miroslav Mikulecký, Iva Subhanová, Pavel Hozák, Milan Jirsa
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 27 Issue 4 Pg. 485-91 (May 2007) ISSN: 1478-3223 [Print] United States
• PMID: 17403188 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCC2 protein, human
• Membrane Transport Proteins
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins
• Sulfobromophthalein

Topics

• Aged
• DNA Mutational Analysis
• Family Health
• Humans
• Hyperbilirubinemia, Hereditary (diagnosis, etiology, genetics)
• Jaundice, Chronic Idiopathic
• Liver (pathology)
• Male
• Membrane Transport Proteins (analysis, genetics)
• Middle Aged
• Multidrug Resistance-Associated Protein 2
• Multidrug Resistance-Associated Proteins (analysis, genetics)
• Sulfobromophthalein (analysis)