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A benign, inherited liver disorder characterized by chronic, predominantly conjugated, nonhemolytic hyperbilirubinemia with normal liver histology.
ORPHA:3111Classification level: Disorder
Rotor syndrome (RT) is a very rare disorder: the exact prevalence is unknown but over 50 cases have been reported in literature so far.
It is usually diagnosed in children or adolescents, but mild jaundice is often noted from birth. The main symptom consists of mild-to-moderate, recurrent jaundice without pruritus. Attacks of abdominal pain and low-grade fever can occur but are rare. Total serum bilirubin (mainly in the conjugated form: 50-80%) is elevated, usually between 2 and 5 mg/dl. Hematologic tests (including measurements of liver enzyme activities) and liver histology are normal. However, absolute and relative concentrations of urinary coproporphyrin I are elevated. Hemolysis is not a feature of the syndrome; however, coinheritance of hemolytic disorders, such as G-6-PD deficiency and beta thalassemia (see these terms), has been reported.
Analysis of the retention of the cholephilic dyes indicates that RT results from a defect in hepatic storage capacity of conjugated bilirubin and other organic cholephilic anions.
As the genetic basis remains unknown and the clinical, biochemical and histological features are non-specific, RT syndrome remains a diagnosis of exclusion. RT should be considered in all patients exhibiting predominantly conjugated hyperbilirubinemia with no concomitant change in liver enzyme activities (i.e. aminotransferases, alkaline phosphatase, and gamma-glutamyl transpeptidase) and in the absence of any septic condition, ultrasound anomaly of the liver or interfering drug. In this context, elevated (250 to 500% higher than controls) urinary concentrations of both total coproporphyrins and coproporphyrin I are very suggestive, but not completely specific for RT. Taken together with these findings, normal liver histology generally allows the diagnosis to be confirmed.
The principle differential diagnosis is Dubin-Johnson syndrome (DJS; see this term). DJS and RT can be distinguished on the basis of measurements of urinary coproporphyrin excretion (total coproporphyrin excretion levels are normal in DJS) and liver histology (black-brown liver cell pigmentation is specific to DJS). If liver biopsy is not feasible or is refused, 99mTc-HIDA cholescintigraphy (revealing prominent kidney excretion in RT) or molecular analysis (detection of ABCC2 gene mutations in DJS patients) can be useful for distinguishing between RT and DJS.
RT appears to be inherited in an autosomal recessive manner, with the parents and siblings of affected individuals showing a pattern of urinary coproporphyrin excretion that is intermediate between that of RT patients and controls.
Management and treatment
As RT is a benign condition, no specific treatment is recommended or generally required. Affected individuals are advised to avoid alcohol and hepatotoxic drugs.
The prognosis for RT patients is good, highlighting the need for correct diagnosis to avoid unnecessary diagnostic procedures, treatment and follow-up. Unless there is a concomitant chronic liver disease, progression to liver failure, cirrhosis or hepatic fibrosis is not observed.
- Clinical genetics review
- English (2019)