Rotor Syndrome

Rotor syndrome is a benign autosomal recessive disorder of hepatic uptake and storage of conjugated bilirubin due to combined deficiency of OATP1B1 and OATP1B3 (SLCO1B1 and SLCO1B3).

• Very rare. Described mainly in the Philippines and Asia.
• Conjugated bilirubin that is synthesised is leaked back into plasma, causing mixed hyperbilirubinaemia.
• Liver histology and gallbladder visualisation are normal (unlike Dubin Johnson syndrome).
• Raises plasma levels of OATP substrates such as statins, methotrexate, irinotecan metabolites, rosuvastatin, bosentan.
• Clinically harmless, life expectancy is normal.

• Mild fluctuating jaundice from childhood or adolescence, with no itching.
• Normal liver size and examination.
• Dark urine, normal stool colour.
• Triggers of exacerbation are infection and fasting.

• Hyperbilirubinaemia of 2 to 5 mg/dL, mostly conjugated (about 50 to 60% direct), normal liver enzymes and albumin.
• Total urinary coproporphyrin markedly elevated (2.5 to 5 times normal), with isomer I about 65% (versus over 80% in Dubin Johnson syndrome, and normal total).
• Oral cholecystography shows normal gallbladder; HIDA scan shows absent or poor hepatic uptake with normal excretion kinetics, and delayed visualisation of liver but biliary tree visible later.
• Liver biopsy normal, no pigment.
• Genetic testing for SLCO1B1 and SLCO1B3 (complete loss of function).
• Exclude Dubin Johnson syndrome, hepatitis, cholestasis, haemolysis.

• No treatment is required, and the condition is benign.
• Counsel the patient and offer genetic counselling.
• Drug safety: avoid or reduce doses of OATP1B substrates: rosuvastatin, atorvastatin, pitavastatin, methotrexate, repaglinide, bosentan, irinotecan (SN-38 exposure), rifampicin. Select alternatives or titrate carefully.
• Avoid estrogen exposure when possible (can raise bilirubin).
• No need for liver biopsy or repeated investigation once diagnosed with typical profile.
• Provide a clinical summary letter to prevent unnecessary surgery or hospital admission.