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.

• Pain

  Showing of 8 | 80%-99% of people have these symptoms Conjugated hyperbilirubinemia 0002908 Jaundice Yellow skin Yellowing of the skin [ more ] 0000952 5%-29% of people have these symptoms Abdominal pain Pain in stomach Stomach pain [ more ] 0002027 Abnormality [rarediseases.info.nih.gov]

  It is characterised by nonhaemolytic jaundice, attacks of intermittent epigastric discomfort and occasionally abdominal pain, and fever. [whonamedit.com]

  He never suffered from abdominal or chest pain, rash, or arthralgia. Major causes of fever were excluded (pulmonary, urinary, abdomen, skin infections, neoplasms, and major rheumatologic disorders). [unboundmedicine.com]

• Fever

  Alpha-1 antitrypsin deficiency c… Publisher Full Text linkinghub.elsevier.comjournals.elsevierhealth.com The grandfather's fever. [unboundmedicine.com]

  It is characterised by nonhaemolytic jaundice, attacks of intermittent epigastric discomfort and occasionally abdominal pain, and fever. [whonamedit.com]

  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. [orpha.net]

  There may be an attack of fever. Diagnosis There is jaundice with increased conjugated bilirubinemia. Liver biopsy is normal in histology. The gallbladder can be visualized by cholecystography. This differentiates it from Dubin-Johnson syndrome. [labpedia.net]

  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. [symptoma.com]

• Malaise

  [Review] Clin Rheumatol 2019Ricci P, Stella A, … Portincasa PCR An 86-year-old Caucasian man had prior episodes of fever (up to 38 °C), mild abdominal pain, tachycardia, and malaise in the last 3 months, lasting 2-3 days. [unboundmedicine.com]

  Acute viral hepatitis often is heralded by anorexia, malaise, myalgias, or discomfort in the epigastrium or right upper abdominal quadrant before jaundice develops (see Chapters 77 to 81 ). Five major hepatitis viruses have been isolated. [clinicalgate.com]

  There was no history of any fever, pruritus, malaise, or abdominal pain. She was non-alcoholic and a non-smoker. There was no history of any blood transfusion, intravenous drug abuse, chronic drug intake, or occupational hazard. [cureus.com]

• Pathologist

  人名（日本語） 使用例（英語） 使用例（日本語） 備考 Aarskog アースコグ Aarskog's syndrome アースコグ症候群 DagfinnAarskog （1928- ） Norwegianpediatrician and human geneticist Adamkiewicz アダムキーヴィッツ Adamkiewicz' artery アダムキーヴィッツ動脈 AlbertWojciech Adamkiewicz （1850-1921） Polish physician and pathologist [jams.med.or.jp]

  Named after : American pathologists, Isadore Dubin and Frank Johnson. Gene/locus : ABCC2 (10q24). Leads to absent function of MRP2 protein, an ATP-dependent canalicular transporter inheritance : Autosomal recessive. [genetics4medics.com]

• Turkish

  Russian Swedish Turkish Ukrainian Chinese Ukrainian These examples may contain rude words based on your search. [context.reverso.net]

  Beckwith-Wiedemann ベックウィズ・ウイーデマン Beckwith-Wiedemann syndrome ベックウィズ・ウイーデマン症候群 John BruceBeckwith （1933- ） Americanpediatric pthologist and Hans-Rudolf Wiedemann （1915- ） German pediatrician Behcet ベーチェット Behcet's disease ベーチェット病 HulusiBehçet, （1889 - 1948） Turkish [jams.med.or.jp]

• Loss of Appetite

  […] of appetite Transient jaundice (varying from mild scleral jaundice to general jaundice) [3] Trigger factors of transient jaundice Physical stress (trauma, disease, exhaustion) Fasting periods Alcohol consumption Diagnosis ↑ Indirect bilirubin but < 3 [amboss.com]

• 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]

  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]

  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 this substance leads to jaundice in people with Rotor syndrome. [3] Eponym Rotor syndrome is named after the Filipino internist, Arturo Belleza Rotor (1907–1988). [4] See also Jaundice Bilirubin metabolism Gilbert's syndrome Crigler–Najjar [ipfs.io]

• Recurrent Jaundice

  Common signs and symptoms include icteric sclera and recurrent jaundice with laboratory findings significant for conjugated and unconjugated hyperbilirubinemia. [visualdx.com]

  Clinical description 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. [orpha.net]

  Progression of Dubin-Johnson syndrome, and Rotor syndrome Both syndromes may present with persistent or recurrent jaundice of variable severity, but most patients exhibit no other symptoms. [healthengine.com.au]

• Scleral Icterus

  Some patients only have scleral icterus. Patients will also complain about passing dark-colored urine. [statpearls.com]

  Some patients only have scleral icterus. Patients also complain about passing dark-colored urine, long-term jaundice, and fatigue. [ncbi.nlm.nih.gov]

  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]

• Pruritus

  Subscription Required Differential Diagnosis & Pitfalls Dubin-Johnson syndrome Progressive familial intrahepatic cholestasis (PFIC) Benign recurrent intrahepatic cholestasis Alagille syndrome Biliary atresia Wilson disease Alpha-1 antitrypsin deficiency Pruritus [visualdx.com]

  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. [orpha.net]

  Patients do not have pruritus. Hepatosplenomegaly occasional. [gastroenterologybook.com]

  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. [symptoma.com]

  Pruritus (without rash) is the chief complaint in intrahepatic cholestasis. Jaundice may occur and typically develops one to four weeks after the onset of symptoms. Pruritus usually disappears within 24-48 hours of delivery [9]. [cureus.com]

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].

• Bilirubin Increased

  Increase unconjugated bilirubin Overproduction Impairment of uptake Defect conjugation of bilirubin Increase conjugated bilirubin Decrease excretion into the bile ductile Backward leakage of the pigment 13. [slideshare.net]

• Liver Biopsy

  Liver biopsy is not required to make the diagnosis of Rotor syndrome, but if done, liver biopsy in patients with the disease reveals normal histology. [statpearls.com]

  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. [symptoma.com]

  Liver biopsy is normal in histology. The gallbladder can be visualized by cholecystography. This differentiates it from Dubin-Johnson syndrome. [labpedia.net]

  Histopathology A liver biopsy is not required to diagnose Rotor syndrome, but if done, a liver biopsy in patients with the disease reveals normal histology. Liver biopsy may help distinguish Rotor syndrome from other, more serious liver diseases. [ncbi.nlm.nih.gov]

  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. [orpha.net]

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 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. [healthengine.com.au]

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]

Natural History Complications Prognosis Diagnosis Diagnostic Criteria History and Symptoms Physical Examination Laboratory Findings Imaging Findings Other Diagnostic Studies Treatment The liver is otherwise normal, and there is no need to treat this [wikidoc.org]

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]

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]

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]

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]

[…] 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]

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]

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.