Rotor type hyperbilirubinemia.
Rotor syndrome is a rare cause of mixed direct (conjugated) and indirect (unconjugated) hyperbilirubinemia.
Caused by mutations in two proteins responsible for transporting bilirubin and other compounds from the blood to the liver to be metabolized and cleared from the body.
The SLCO1B1 and SLCO1B3 genes are involved in Rotor syndrome.
Both proteins are found in liver cells; they transport bilirubin and other compounds from the blood into the liver so that they can be cleared from the body.
The SLCO1B1 and SLCO1B3 gene mutations that cause Rotor syndrome lead to abnormally short, nonfunctional OATP1B1 and OATP1B3 proteins or an absence of these proteins.
Without the function of either transport protein, bilirubin is less efficiently taken up by the liver and removed from the body.
Mutations in both genes are required for the condition to occur.
It is a relatively benign, autosomal recessive bilirubin disorder characterized by non-hemolytic jaundice due to the chronic elevation of predominantly conjugated bilirubin.
It is a distinct, yet similar, disorder to Dubin–Johnson syndrome, as both diseases cause an increase in conjugated bilirubin.
Whereas rotor syndrome differs in that it is a result of impaired hepatocellular storage of conjugated bilirubin that leaks into plasma causing hyperbilirubinemia.
It has many features in common with Dubin–Johnson syndrome, an exception being that the liver cells are not pigmented.
The main symptom is a non-itching jaundice.
There is an increased bilirubin in the patient’s serum: mainly of the conjugated type.
The liver has a normal histology and appearance vs black appearing liver with Dubin-Johnson syndrome.
The gallbladder can be visualized by oral cholecystogram, but this is not the case with Dubin-Johnson syndrome.
Rotor syndrome may exacerbate toxic side effects of the medication irinotecan.
Coproporphyrin I, a major coproporphyrin isomer in bile, is transported from the hepatocyte back into the circulation and is excreted in the urine: it is elevated in Rotor syndrome.
Cholescintigraphy using sulfobromophthalein (BSP) have shown that the transport capacity of dye into bile is reduced by less than 50%, and the storage capacity in the hepatocytes is decreased more than 5-fold compared with normal values.
In the liver, bilirubin is dissolved in bile and then excreted from the body.
The buildup of bilirubin leads to jaundice in people with Rotor syndrome.
DIAGNOSIS:
Increased conjugated hyperbilirubinemia is the hallmark for diagnosis.
Genes, SLCO1B1 and SLCO1B3 that result in complete functional deficiencies of both protein products (OATP1B1 and OATP1B3, respectively), are also present.
IT is largely a diagnosis of exclusion.
Elevated total serum bilirubin: between 2 to 5 mg/dL but may be as high as 20 mg/dL.
Most of the time, liver functions are normal, but mild elevations can be seen.
The best method of diagnosing the disease is the analysis of urine coproporphyrin excretion.
The total urine coproporphyrin excretion in Rotor syndrome has a 2- to 5-fold elevation, with 65% constituting coproporphyrin I.
Treatment:
Rotor syndrome is a benign disease requiring no treatment.
Jaundice is a lifelong finding.
The disease is not associated with morbidity or mortality, and life expectancy is not affected.
Most individuals with Rotor syndrome are born to consanguineous couples.