Dubin-Johnson and Rotor Syndromes: A Review and Update of Pathophysiological Mechanisms

Area of Science:

• Hepatology
• Medical Genetics
• Biochemistry

Background:

• Dubin-Johnson syndrome (DJS) and Rotor syndrome (RS) are rare, autosomal recessive disorders characterized by chronic conjugated hyperbilirubinemia.
• These conditions are benign and non-progressive, but stem from distinct molecular defects in hepatocellular transport pathways.

Purpose of the Study:

• To review current evidence on DJS and RS, focusing on molecular defects, clinical distinctions, and broader implications for hepatic transporter physiology.
• To highlight the importance of recognizing DJS and RS to prevent misdiagnosis and manage altered pharmacokinetics.

Main Methods:

• Review of molecular, biochemical, and clinical studies.
• Analysis of genetic mutations in ABCC2 (DJS) and SLCO1B1/SLCO1B3 (RS) genes.
• Comparison of clinical and biochemical features distinguishing DJS and RS.

Main Results:

• DJS results from ABCC2 mutations impairing canalicular excretion of conjugated bilirubin and organic anions.
• RS stems from deficiencies in OATP1B1 and OATP1B3, affecting hepatic reuptake of conjugated bilirubin.
• Distinct features include black liver pigmentation and elevated urinary coproporphyrin I in DJS, versus no pigmentation and moderate coproporphyrin I predominance in RS.

Conclusions:

• DJS and RS offer insights into hepatic transporter function and bilirubin metabolism.
• Accurate diagnosis is crucial for appropriate patient management, avoiding unnecessary investigations for cholestatic or hepatocellular disease.
• Understanding these syndromes is vital for predicting drug pharmacokinetics and managing inherited/acquired bilirubin metabolism disorders.