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 [1].

Rotor syndrome remains at this time a diagnosis of exclusion.

• Sucrose Intolerance

  […] uridylyltransferase galactosemia, Galactokinase deficiency) - other intestinal carbohydrate absorption (Glucose-galactose malabsorption, Sucrose intolerance) - pyruvate metabolism and gluconeogenesis (PCD, PDHA) - Pentosuria - Renal glycosuria Lipid [wikidoc.org]

• Jaundice

  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]

  Rotor syndrome - jaundice appearing in childhood due to impaired biliary excretion. [medical-dictionary.thefreedictionary.com]

  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]

  Jaundice is caused by hyperbilirubinemia, or abnormally high levels of bilirubin in the blood. Bili lights may also be used to treat newborn jaundice ( hyperbilirubinemia ). [diki.pl]

  In favor of the latter is the observation that our patients initially had jaundice at birth. [journals.lww.com]

• Scleral Icterus

  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 [2].

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 [3]. 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 [4] 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 [5]. Genetic differential diagnosis with Dubin-Johnson syndrome is also possible [6] [7].

• Capillaria Philippinensis

  philippinensis: case report and review of literature. 61 Helmy H...El-Karaksy H 21980780 2011 27 Dubin-Johnson syndrome presenting after acute viral hepatitis. 61 Lahmi F...Zali MR 24834177 2011 28 Hyperbilirubinemia syndromes (Gilbert-Meulengracht, [malacards.org]

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]

Treatment of Rotor Syndrome No treatment is needed. Written by Dr Sebastian Zeki [gastroenterologybook.com]

To the best of our knowledge, there is no information in the literature relating to the treatment of a patient with colon cancer and RS. [spandidos-publications.com]

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]

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.co.uk]

Hyperbilirubinemia is an important clinical sign that often indicates severe hepatobiliary disease of different etiologies. [ncbi.nlm.nih.gov]

♂ > ♀ Age of onset: adolescence Etiology Mutation in the promoter region of UGT1A1 gene → ↓ activity of UDP-glucuronosyltransferase→ decreased conjugation of bilirubin → ↑ indirect bilirubin Autosomal recessive inheritance Clinical features Asymptomatic [amboss.com]

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]

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.[1] There are no available population-based figures for its prevalence or incidence: It appears to be most common in the Philippines, where [patient.info]

Allowable Qualifiers English : BL blood CF cerebrospinal fluid CI chemically induced CL classification CO complications DI diagnosis DG diagnostic imaging DH diet therapy DT drug therapy EC economics EM embryology EN enzymology EP epidemiology EH ethnology [decs.bvs.br]

[…] 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]

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]

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. [ghr.nlm.nih.gov]

Pathophysiology This is a rare, relatively benign (mild) autosomal recessive disease of the liver. This is similar to Dubin-Johnson syndrome and both leads to increase conjugated (direct) bilirubin. [labpedia.net]

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]

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]

In the liver, bilirubin is dissolved in a digestive fluid called bile, and then excreted from the body. [2] The mutations in the S LCO1B1 and SLCO1B3 genes that cause Rotor syndrome either prevent the production of the transporting proteins, or prevent [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]

1. 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.
2. Strassburg CP. Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome). Best Pract Res Clin Gastroenterol. 2010;24(5):555–571.
3. Nowicki MJ, Poley JR. The hereditary hyperbilirubinaemias. Baillieres Clin Gastroenterol. 1998;12(2):355–367.
4. LeBouthillier G, Morais J, Picard M, et al. Scintigraphic aspect of Rotor‘s disease with Technetium-99m-mebrofenin. J Nucl Med. 1992;33(8):1550–1551.
5. 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.
6. 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.
7. Paulusma C. A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome. Hepatology. 1997;25(6):1539–1542.