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Rotor Syndrome

Hyperbilirubinemia Idiopathic

Rotor syndrome is a liver disorder consisting of conjugated nonhemolytic hyperbilirubinemia, with no underlying organic liver abnormalities. It is transmitted in an autosomal recessive manner.


Presentation

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.

Camping
  • […] mutation of CF transmembrane conductance regulator on chromosome 7 *normal fx: phosphorylation of CFTR by protein kinase A using cAMP controls the chloride channel in the apical membranes of eccrine glands.[quizlet.com]
  • ネルソン Nelson syndrome ネルソン症候群 Nicolas-Favre ニコラ・ファーブル Nicolas-Favre disease ニコラ・ファーブル病 Niemann-Pick ニーマン・ピック Niemann-Pick disease ニーマン・ピック病 AlbertNiemann (1880-1921) German pediatrician and Ludwig Pick (1868-1944) Germanpathologist died in concentrate camp[jams.med.or.jp]
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]
  • 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]
  • It is characterised by nonhaemolytic jaundice, attacks of intermittent epigastric discomfort and occasionally abdominal pain, and fever.[whonamedit.com]
Scleral Icterus
  • 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]

Workup

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].

Atelectasis
  • […] marked hyperplasia and hypertrophy List 2 consequences of bronchiolar plugging in cystic fibrosis. atelectasis (resorptive) emphysema due to destruction of parenchyma List 3 consequences of lung infections in cystic fibrosis. chronic bronchitis bronchiectasis[quizlet.com]

Treatment

  • 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]
  • Significant updates on bariatric surgery, Barrett's esophagus, endoscopic ultrasound, endosonography, treatment of liver disease, and much more keep you current on the latest advances.[books.google.de]

Prognosis

  • 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]
  • 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]
  • Prognosis Usually good with a benign course, unless there is coexistent liver disease. Did you find this information useful? yes no Limdi JK, Hyde GM ; Evaluation of abnormal liver function tests. Postgrad Med J. 2003 Jun79(932):307-12.[patient.info]

Etiology

  • Infectious etiology of jaundice, autoimmune diseases, drug-induced liver injury, hemolytic anemia, α-1 anti-trypsin deficiency, Wilson disease and Gilbert syndrome were ruled out.[ncbi.nlm.nih.gov]
  • Hyperbilirubinemia is an important clinical sign that often indicates severe hepatobiliary disease of different etiologies.[ncbi.nlm.nih.gov]
  • This is the first documented case of a population-specific polymorphic intronic L1 transposon insertion contributing to molecular etiology of recessive genetic disease.[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]
  • Age of onset: adolescence Etiology Mutation in the promoter region of UGT1A1 gene activity of UDP-glucuronosyltransferase decreased conjugation of bilirubin indirect bilirubin Clinical features Asymptomatic or unspecific symptom s such as fatigue and[amboss.com]

Epidemiology

  • 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]
  • […] visualized total urine coproporphyrin content high with 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]
  • 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]
  • Classification Gilbert's syndrome (Gilbert-Meulengracht syndrome; Meulengracht disease) Epidemiology Most common inherited hyperbilirubinemia : The prevalence is 3–7% in the US.[amboss.com]
Sex distribution
Age distribution

Pathophysiology

  • 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 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]
  • Reinforce your foundation in basic science with the concise Pathophysiology of Therapeutic Targets section. See clear presentations of liver disease through hundreds of detailed, color illustrations.[books.google.de]

Prevention

  • […] the production of the transporting proteins, or prevent them from functioning properly.[rarediseases.info.nih.gov]
  • 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]
  • Medical Therapy Surgery Prevention Eponym Rotor syndrome is named after the Filipino internist, Arturo Belleza Rotor (1907-1988). [1] See also Jaundice Bilirubin metabolism Dubin-Johnson syndrome Gilbert syndrome Crigler-Najjar syndrome References External[wikidoc.org]
  • Its co-occurrence with the 405-kb R2 deletion in two asymptomatic family members (Table 1 ) indicates that a single functional SLCO1B3 allele can prevent RS.[doi.org]

References

Article

  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.

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Last updated: 2019-07-11 22:02