The diagnosis of Rotor syndrome is usually made during childhood or adolescence, based on the presence of skin and scleral jaundice with no pruritus, unlike other cholestatic syndromes. But the disease can also be present in newborns, where high levels of bilirubin can lead to encephalopathy and kernicterus if bilirubin level is above 20 mg/dL. The latter can also be encountered in young adults with increased unconjugated bilirubin, as a consequence of Rotor syndrome or an enzyme such as bilirubin-UDP-glucuronyltransferase deficiency. Icterus may be permanent or intermittent. The disease may have acute episodes, characterized by abdominal pain and low-grade fever. Between acute episodes, the clinical examination of Rotor syndrome patients is normal, other than the presence of icterus.
Because of the clinical similarities, Rotor syndrome and Dubin-Johnson syndrome were thought to be the same pathological entity, until paraclinical data in the late 1970s proved that they were, in fact, different conditions .
Rotor syndrome remains at this time a diagnosis of exclusion.
Entire Body System
Liver, Gall & Pancreas
Jaundice Bilirubin metabolism Gilbert's syndrome Crigler–Najjar syndrome Hyperbilirubinemia, Conjugated at eMedicine Rotor syndrome at NIH's Office of Rare Diseases Mentioned in MedlinePlus Encyclopedia Jaundice – yellow skin [en.wikipedia.org]
It has an orange-yellow tint, and buildup of this substance can cause yellowing of the skin or whites of the eyes (jaundice). [ghr.nlm.nih.gov]
The buildup of bilirubin in the body causes yellowing of the skin or whites of the eyes ( jaundice ), which is the only symptom of the disorder. Jaundice is usually evident in infancy or early childhood, and it may come and go. [rarediseases.info.nih.gov]
Rotor syndrome - jaundice appearing in childhood due to impaired biliary excretion. [medical-dictionary.thefreedictionary.com]
Some patients only have scleral icterus. Patients will also complain about passing dark-colored urine. [statpearls.com]
Unlike true jaundice, carotenemia does not result in scleral icterus or elevation of the bilirubin level. 8 PREHEPATIC CAUSES Unconjugated hyperbilirubinemia results from a derailment of the necessary bilirubin conjugation in the hepatocyte. [aafp.org]
Blood workup usually shows no abnormalities of aminotransferase, gamma-glutamyl transpeptidase, prothrombin time and alkaline phosphatase levels, although occasional mild increases may be found. Blood bilirubin level is high, usually 2 to 5 mg/dL, but may be as high as 20 mg/dL. Serum bile acid levels are normal. Hemolysis is absent in typical cases, although cases with concomitant hemolytic disorders, such as G-6-PD deficiency and beta thalassemia were described. Still, it can be useful to perform hemolysis tests, such as hemoglobin, reticulocyte count, haptoglobin level and blood smear, which will all be normal. Plasma clearance of bromsulfthalein is delayed because the capacity to transport this product into the bile is reduced by half .
Urinary workup shows markedly increased concentrations of total coproporphyrins and coproporphyrin I. Urinary coproporphyrin is around 65% in homozygotes and 40% in heterozygotes. Coproporphyrin I will account for 65% of total coproporphyrin level, the rest consisting of coproporphyrin III.
Imaging methods used in Rotor syndrome consist of ultrasonography and cholecystography. Hepatic ultrasound imaging is normal in this condition . It should be performed in order to exclude extrahepatic biliary obstruction. Cholecystography is able to visualize the gall bladder in Rotor syndrome. In doubtful cases, a cholescintigraphy with 99mTc-dimethyl acetanilide iminodiacetic acid or Technetium-99m-mebrofenin scintigraphy  can be performed. These investigations will show a faint uptake, similar to patients with hepatocellular disease. Differentiation between these two categories will be done using blood workup.
Less used tests in this condition include liver biopsy and genetic panel. If a liver biopsy is considered to be necessary, normal liver histology will be found in Rotor syndrome. No hepatocyte pigment deposits are described in this condition. Liver biopsy is also useful for excluding other conditions. Genetic tests in affected individuals can detect two mutations in the SLCO1B1 gene and SLCO1B3 gene. Simultaneous mutation in both genes is necessary in order to produce the disease . Genetic differential diagnosis with Dubin-Johnson syndrome is also possible  .
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. [orpha.net]
You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments. [rarediseases.info.nih.gov]
Inherited non-haemolytichyperbilirubinemic conditions include Dubin-Johnson, Rotor, and Gilbert-Meulengracht syndromes, which are important differential diagnoses indicating benign disease that require no immediate treatment. [ncbi.nlm.nih.gov]
Treatment of Rotor Syndrome No treatment is needed. Written by Dr Sebastian Zeki [gastroenterologybook.com]
Prognosis The prognosis for RT patients is good, highlighting the need for correct diagnosis to avoid unnecessary diagnostic procedures, treatment and follow-up. [orpha.net]
Prognosis of Dubin-Johnson syndrome, and Rotor syndrome Prognosis is excellent and life expectancy is normal in both syndromes. How is Dubin-Johnson syndrome, and Rotor syndrome Treated? No specific treatment is required. [myvmc.com]
The prognosis is excellent. Links: Dubin-Johnson syndrome [gpnotebook.com]
Hyperbilirubinemia is an important clinical sign that often indicates severe hepatobiliary disease of different etiologies. [ncbi.nlm.nih.gov]
Etiology 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. [orpha.net]
While the etiology of RS is not well known, it has been suggested that the condition occurs as a result of a complete lack or partial defect of organic anion transporter polypeptides (OATPs) on the basolateral surface of hepatocytes. [spandidos-publications.com]
Patient Population: Prevalence and Epidemiology Knee // Shoulder & Elbow // Hip // Spine // Foot & Ankle // Hand & Wrist Fragility Fractures: Diagnosis and Treatment Shoulder & Elbow The Characteristics of Surgeons Performing Total Shoulder Arthroplasty [mdedge.com]
Summary Epidemiology Rotor syndrome (RT) is a very rare disorder: the exact prevalence is unknown but over 50 cases have been reported in literature so far. [orpha.net]
Epidemiology It occurs sporadically in families and is thought to be inherited in an autosomal recessive fashion. There are no available population-based figures for its prevalence or incidence: It appears to be most common in the Philippines, where [patient.info]
[…] coproporphyrin content high with 70% being isomer 1 normal with 80% being isomer 1 (normal urine contains more of isomer 3 than isomer 1) Historical Perspective Classification Pathophysiology Causes Differentiating Rotor syndrome from Other Diseases Epidemiology [wikidoc.org]
OATP1B1 and OATP1B3 proteins are abnormally short; therefore, the bilirubin is less efficiently taken up by the liver and removed from the body, causing a buildup of bilirubin in the blood and urine which results in jaundice and dark urine. Epidemiology [statpearls.com]
With respect to urinary coproporphyrin excretion, Rotor's syndrome and Dubin-Johnson syndrome are both inherited as autosomal recessive traits and are separate pathophysiologic entities. [ncbi.nlm.nih.gov]
A distinct inheritable pathophysiologic entity. Am J Med 60(2):173–179 PubMed Google Scholar 4. Berthelot P, Dhumeaux D (1978) New insights into the classification and mechanisms of hereditary, chronic, non-haemolytic hyperbilirubinaemias. [link.springer.com]
A distinct inheritable pathophysiologic entity. [ghr.nlm.nih.gov]
Pathophysiology 2) BMJ Publishing Group Limited Four inherited hyperbilirubinemias: Crigler-Najjar, Gilbert, Dubin-Johnson and Rotor syndrome Dye clearance studies using sulphobromophthalein (BSP) have shown that in Rotor’s syndrome, the transport capacity [meddiction.com]
[…] pigmentation.1 2 3 4 Because of clinical similarities, Rotor's syndrome has been considered to be a variant of the Dubin-Johnson syndrome.2, 3, 5 Recent studies of urinary coproporphyrin excretion, however, demonstrate that the two syndromes are distinct pathophysiologic [nejm.org]
Within liver lobules, this shuttle may allow flexible transfer of bilirubin conjugates (and probably also drug conjugates) formed in upstream hepatocytes to downstream hepatocytes, thereby preventing local saturation of further detoxification processes [ncbi.nlm.nih.gov]
[…] the production of the transporting proteins, or prevent them from functioning properly. [rarediseases.info.nih.gov]
(Hum Mutat 36:327–332, 2015) report an unusual mutation in Rotor Syndrome, an autosomal recessive disorder in which bilirubin is prevented from entering the hepatocyte prior to its excretion in the bile. [onlinelibrary.wiley.com]
- Wolpert E, Pascasio F, Wolkoff A, et al. Abnormal sulfobromophthalein metabolism in Rotor's syndrome and obligate heterozygotes. New Eng. J. Med. 1977;296: 1099-1101.
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- van de Steeg E, Stranecky V, Hartmannova H, et al. Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J. Clin. Invest. 2012;122: 519-528.
- Kartenbeck J, Leuschner U, Mayer R, et al. Absence of the canalicular isoform of the MRP gene-encoded conjugate export pump from the hepatocytes in Dubin-Johnson syndrome. Hepatology. 1996;23(5):1061–1066.
- Paulusma C. A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome. Hepatology. 1997;25(6):1539–1542.