Rotor’s Syndrome: A family study

@#A family was studied in which three members in the sibship belonging to the fourth generation were found to have Rotor’s syndrome. More detailed examinations including blood studies, liver profiles, oral cholecystograms, and liver biopsies where performed on the affected siblings. The results were related to what is at present known about the features and mechanisms of Rotor’s syndrome, pari passu the current concept of bilirubin metabolism. It is suggested that the constant finding, and possibly the only characteristic one in Rotor’s syndrome, is the absence of abnormal hepatic cell pigmentation. Pedigree analysis of the present family shows that the transmission of this disorder may be conditioned by an autosomal recessive gene.

Analysis of genetic variants in a case with Rotor syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a patient featuring Rotor syndrome.@*METHODS@#Clinical data of the patient was collected. Whole exome sequencing (WES) based on high-throughput sequencing technology was carried out. Long-interspersed element-1 (LINE-1) insertion in intron 5 of the SLCO1B3 gene was detected by using tri-primer single tube PCR.@*RESULTS@#WES revealed that the patient has carried homozygous c.1738C>T nonsense variants of the SLCO1B1 gene. He was also found to harbor a homozygous insertion of LINE-1 in intron 5 of the SLCO1B3 gene, which has caused skipping of exon 5 or exons 5 to 7 and introduced a stop codon in the SLCO1B3 transcript.@*CONCLUSION@#The homozygous c.1738C>T variant of the SLCO1B1 gene and homozygous insertion of LINE-1 in intron 5 of the SLCO1B3 gene probably underlay the Rotor syndrome in this patient.

Hiperbilirrubinemias hereditarias: un diagnóstico diferencial a considerar en ictericia / Hereditary hiperbilirrubinemias: a differential diagnosis to considerer in icterus

Las hiperbilirrubinemias hereditarias (HBH) son patologías originadas por defectos en las enzimas y proteínas que participan del metabolismo de la bilirrubina. El clearence de bilirrubina incluye captación y almacenamiento en hepatocitos, conjugación, excreción hacia la bilis y recaptura de su forma conjugada por hepatocitos. Las HBH varían de acuerdo a su patogenia, presentación clínica, niveles de bilirrubinemia y tratamientos disponibles. En general son poco frecuentes, a excepción del Síndrome de Gilbert. Están las que son de predominio indirecto, como el Síndrome de Gilbert y el de Crigler-Najjar, y las de predominio directo, como el Síndrome de Dubin-Johnson y el de Rotor. En general no requieren tratamiento específico y tienen curso benigno, a excepción del Síndrome de Crigler-Najjar para el cual existen medidas terapéuticas específicas a considerar, teniendo un pronóstico reservado para algunas de sus formas de presentación. Es importante el conocimiento de estos síndromes dado el alto índice de sospecha requerido para su diagnóstico y para su diferenciación de otras patologías hepatobiliares de mayor riesgo y severidad.

Hereditary hiperbilirrubinemias (HBH) are pathologies originated from the defect of the enzymes and proteins involved in the metabolism of bilirubin. The bilirubin clearance includes uptake and storage in hepatocytes, conjugation, excretion into bile and recapture of its conjugated form by hepatocytes. HBH vary according to their pathogenesis, clinical presentation, levels of bilirubin and available treatments. Generally they are infrequent, except for Gilbert Syndrome. There are those with indirect bilirubin predominance, such as Gilbert and Crigler-Najjar syndromes, and those with direct bilirubin predominance, including Dubin-Johnson and Rotor syndromes. In general, they do not require specific treatment and have a benign course, with the exception of the Crigler-Najjar Syndrome, for which there are specific therapeutic measures to consider, as well as a reserved prognosis for some of their forms of presentation. The knowledge of these syndromes is important 2 given the high index of suspicion required for its diagnosis and for its differentiation from other hepatobiliary pathologies of greater risk and severity.

Hiperbilirrubinemia indirecta de origen genético: informe de un caso de síndrome de Crigler-Najjar de tipo II / Indirect hyperbilirubinemia of genetic origin: case report of Crigler-Najjar syndrome type II

El síndrome de Crigler Najjar II aparece por un déficit en la conjugación de la bilirrubina debido a la deficiencia parcial de la enzima uridindifosfato-glucuronil transferasa. Por lo general, tiene un curso benigno, a diferencia del Crigler Najjar de tipo I, donde el déficit enzimático es total y los afectados mueren a edades tempranas. Se presenta el caso de una adolescente de16 años con hiperbilirrubinemia indirecta, síndrome convulsivante y parálisis cerebral. Una correcta historia clínica con estudio genealógico y pruebas funcionales apropiadas, permitieron determinar el diagnóstico definitivo. Esta enfermedad genética se transmite de forma autosómica recesiva, tiene una prevalencia muy baja a nivel mundial y constituye, en general, un reto diagnóstico para los médico.

Crigler Najjar syndrome type II is related to a defect of bilirubin conjugation due to partial deficiency of the enzyme uridine diphosphate-glucuronyl transferase. Usually has a benign course, unlike Crigler Najjar type I, where the enzyme deficiencyis total and the affected patients usually die at early ages. We present the case of a teenager with indirect hyperbilirubinemia, seizures and cerebral palsy. A good clinical historywith pedigree and appropriate functional tests allowed us to determine the definitive diagnosis. This is an autosomal recessive disorder, has a very low prevalence worldwide, and is adiagnostic challenge for physicians in general.

study of a new method in treatment of term newborns with non-hemolytic hyperbilirubinemia

The purpose of the study was to determine whether reduction of serum levels of bilirubin is more in full-term newborn with non-hemolytic hvperbilirubinemia that treated with new treatment than in matched control subjects. Eighty consecutively admitted term health neonate with indirect hvperbilirubinemia and indication for phototherapy were randomized into receiving phenobarbital [3 mg/kg/day] plus phototherapy as new treatment method or phototherapy as routine method after obtaining intformed consent. The neonate followed up until discharge. The total serum bilirubin levels were measured four times a day. Patient's data regarding variation of bilirubin and hospitalization duration collected and compared from the two groups. Results are presented as the mean, 95% confidence interval, 0.05% significance level and 80% power The baseline characteristics were similar in two groups. Mean ages were 5.5 +/- 2.81 and 4.80 +/- 1.68 days for control and case group respectively. Mean bilirubin levels in admission were l 9.48 +/- 2.80 mg/dl and 18.51 +/- 166 for control and case group respectively. There was significant reduction of bilirubin levels in case group compared to control group [10.54 +/- 3.00 mg/dl versus 8.60 +/- 1.99 mg/dl] [P=0.001]. No significant difference with respect to duration of hospitalization was observed in two groups' [2.05 +/- 0.59 days for control versus, 2.15 +/- 0.80 days for case group]. In despite of significant reduction of bilirubin levels in case group compared to control group, combined treatment is not helpful in reducing of hospitalization days of non-hemolytic hyperbilirubinemia in healthy term neonates

effect of clofibrate on neonatal jaundice

Hyperbilirubinemia is a common problem in newborn infants and may progress to kernicterus if not treated. The objective of this study was to determine the therapeutic effect of clofibrate in full-term healthy neonates with non-hemolytic hyperbilirubinemia. A randomized clinical trial was performed on two groups of healthy full-term neonates with jaundice. Clofibrate group, [n = 50], received a single dose of oral clofibrate [100 mg/kg], plus phototherapy, while the control group [n = 50], received only phototherapy. The mean plasma total bilirubin levels at 12, 24, and 48 hours after treatment were significantly lower in the clofibrate treated group, as compared with the control group [p = 0.001]. At 48 hours of treatment, 48% of patients in the clofibrate group, had bilirubin levels < 12 mg/dl in comparison with 16% of control group [p = 0.001]. Treatment with elfibrate also resulted in a shorter duration of hospital stay as compared to control group [P = 0.001]. A single oral dose of clofbrate [100 mg/kg] along with photo therapy is more effective than photo therapy alone in treatment of non-haemoly tic hypoerbilirution emia in full-term healthy newborn in fants

Ictericia recurrente en hombre de 22 años: presentación de un caso de esferocitosis hereditaria / A case of hereditary spherocytosis presenting with recurrent jaundice in a 22 year-old man

Se presenta el caso de un hombre joven con ictericia, hiperbilirrubinemia severa y fiebre. La evidencia de esferocitos en sangre periférica y las pruebas de fragilidad osmótica aumentada sugieren el diagnóstico de esferocitosis hereditaria. La hiperbilirrubinemia es producida por hemólisis, la cual resulta de un proceso infeccioso. Una vez hecho el diagnóstico, la respuesta al tratamiento es favorable.A case of a young man with jaundice, severe hyperbilirubinemia and fever is presented. Evidence of spherocytes on peripheral blood smear and increased osmotic fragility test suggest the diagnosis of hereditary spherocytosis. The hyperbilirubinemia is produced by hemolysis which is the result of an infectious process. Once the diagnosis is done the answer for the treatment is favorable

A Case with Rotor Syndrome in Hyperbilirubinemic Family / 대한소화기학회지

Rotor syndrome is a rare, benign familial disorder characterized by chronic fluctuating, nonhemolytic and predominantly conjugated hyperbilirubinemia with normal hepatic histology. In contrast to Dubin-Johnson syndrome, there is no liver pigmentation in Rotor syndrome. A 36-year-old man was admitted due to asymptomatic persistent jaundice. His siblings had jaundice with direct hyperbilirubinemia. Physical examination revealed icteric sclerae without hepatosplenomegaly. Laboratory findings showed increased serum bilirubin with direct bilirubinmia. Hepatic uptake and storage capacity of indocyanine green was markedly reduced, while excretion into bile was slightly suppressed. Markedly decreased hepatic uptake and poor visualization of the gallbladder and biliary tract were shown in 99mTc-DISIDA scan. Histology of the liver showed mild steatosis without pigmentation. We report a case with the review of literature.

Comparison of di-isopropyl iminodiacetic acid with methyl isobutyl isonitrile in the work-up of infants with prolonged jaundice

The study group comprised of 16 jaundiced children [mean age 3.16 months] with bilirubin levels of more than 8mg/dl. The clinical differential diagnosis included biliary atresia versus neonatal hepatitis. Informed consent was taken from all the parents. Parents were advised to omit the morning feed. All children were pretreated with phenobarbitone [5mg/ kg/day for 5 days] and imaged twice on two different days: first with Tc-99m-DISIDA and dose of 37MBq was injected intravenously. Liver images were obtained at 1, 2, 3 and 24 hours following injection. Then injection of Tc-99m-MIBI with a dose of 37MBq was injected intravenously. Anterior abdominal images with 350k counts were obtained at 10, 20, 30 and 40 minutes post injection and where appropriate delayed additional views were taken to optimize radionuclide intestinal transit. Two nuclear medicine physicians visually analyzed the scintigrams. On the basis of biliary-enteric kinetics the patients were subdivided into sub-groups: Group 1: Included 12 patients with no bowel activity with DISIDA scan but demonstrable bowel activity with MIBI liver scan with the appearance of central or peripheral abdominal activity. Group 2: Consisted of 4 patients with no bowel activity with both DISIDA and MIBI liver scans. Of the 4 patients 2 had biliary atresia confirmed at laparotomy whilst 2 children were lost to follow-up since the children had traveled from remote parts of the country

Two Cases of Rotor Syndrome in Siblings / 소아과

Rotor syndrome is a rare benign familial disorder characterized by chronic, fluctuating, nonhemolytic and predominantly direct bilirubinemia with normal liver tissue. We have recently experienced two cases of Rotor syndrome in a brother and sister. They revealed icteric sclerae with mild hepatomegaly in physical examination. Laboratory findings showed increased serum bilirubin with direct bilirubin predominance. The urinary excretion of total coproporphyrin was slightly elevated. The 99mTc-DISIDA scan showed a markedly decreased hepatic uptake and poor visualization of gallbladder and biliary tree which could be compatible to the Rotor syndrome. We report two cases with a review of the literature.

Two Cases of Rotor Syndrome in Siblings / 대한소아소화기영양학회지

We experienced two cases of Rotor syndrome in brothers who were a 13 year-old boy and an 11 year-old boy, respectively. They presented with icteric scleras for a few months. Their common laboratory characteristics were as follows: Direct bilirubin was more increased than indirect bilirubin, but aminotransferases were normal. Plasma indocyanine green (ICG) test revealed hepatic excretory defect: plasma ICG concentrations 15 minutes after intravenous injection were 80.45% and 78.28%, respectively. 99mTc-DISIDA Hepatobiliary scan showed that severely decreased hepatic extraction with mild cardiac blood pool, markedly delayed biliary excretion in both intra- & extra- hepatic bile ducts, delayed visualization of gall bladder, and markedly delayed intestinal biliary passage. Needle liver biopsy showed normal hepatic histology without pigmentation.

A case of rotor syndrome / 대한내과학회지

Rotor syndrome is a rare benign familial disorder characterized by chronic, fluctuating, nonhemolytic and predominantly conjugated hyperbilirubinemia with normal liver tissue. In contrast to Dubin-Johnson syndrome, there is no liver hyperpigmentation in Rotor syndrome, and BSP clearance does not show a secondary retention peak. The serum bilirubin in patients with Gilbert's syndrome is almost all unconjugated in contrast to Rotor syndrome. A 29-year-old male was admitted due to persistent jaundice. Physical examination revealed icteric sclera without hepatosplenomegaly. Laboratory findings showed increased serum bilirubin with indirect bilirubin predominance. Urinary excretion of total coproporphyrin was markedly elevated, and coproporphyrin I was 66% of total urinary coproporphyrin. Oral cholecystography showed well visualized the gallbladder, but 99mTc-DISIDA scan showed markedly decreased hepatic uptake and poor visualization of the gallbladder and biliary tract. Histology of the liver showed no abnormal finding. We report the case with the review of literature.

Three Cases of Rotor Syndrome in Monozygotic Twin Brothers and Their Sister

No abstract available.

A Case of Rotor Syndrome

We experienced a case of Rotor syndrome in an 8 year 6 month old boy who presented with icteric sclera and icteric skin on whole body. His clinical and laboratory characteristics were as follows; 1) Jaundice appeared from several months ago before admission without any clinical disturbance. 2) Direct bilirubin was more increased than indirect bilirubin. 3) Plasma indocyanine green (ICG) kinetics test revealed hepatic excretory in this patient that after intravenous injection of a standard dose of ICG (0.5mg/kg), its initial plasma disappearance is decreased, resultin in markedly increased retention of the dye 45 to 50 minutes after administration. 4) Oral cholangiography, ultrasonogram, and computed tomogram of abdomen were normal. 5) Liver biopsy specimen showed no dark brown pigmentations in the hepatic cells and any other pathologic abnormalities. 6) Nearly similar clinical and laboratory findings were observed 26 months later.

Estados críticos neonatales e hiperamonemia / Critical care neonatal and hyperammonemia

En el presente trabajo de investigación se determinan las concentraciones del amonio plasmático, mediante la espectrofotometría cuantitativa ultravioleta de la Sigma Technical Co. en 300 neonatos de distintos pesos y edades gestacionales al nacer, manejados diagnóstica y terapeúticamente por presentar estados críticos y patológicos, atendidos en salas de parto y de "alto riesgo" en el servicio de Neonatología de la Maternidad Dr. Armando Castillo Plaza. Se distribuyeron en 5 categorías con dos grupos en cada una, en base al tipo de neonato (pretérmino o a término), Categoría A: 75 neonatos con hipoxia fetoneonatal; registraron cifras de amonio plasmático (mcg/ml) (0-6; 0-24; 24-72 horas de vida) A1: a término X 3,690 - X 2,480 - X 1,940. A2: pretérmino X 3,480 - X 2,360 - X 1,850. Categoría B: 50 neonatos con dificultad respiratoria aguda registraron cifras de amonio plasmático (mcg/ml) (0-6; 6-24; 24-72 horas de vida); B1: a término X 2,670 - X 1,920 - X 1,340. B2: pretérmino X 3,502 - X 2,320 - X 1,640. Categoría C: 50 neonatos con sepsis registraron cifras de amonio plasmático (mcg/ml) (0-72; 72-120; 120-180 horas de vida); C1: a termino X 2,270 - X 1, 690 - X 1,250. C2: pretérmino X 2,900 - X 2,320 X 1,500. Categoría D: 50 neonatos nacidos policitémicos con hiperviscocidad sanguínea registraron cifras de amonio plasmático (mcg/ml) (0-6; 6-24; 24-72 horas de vida); D1: a término X 2,150 - X 1,880 - X 1,290. D2: pretérmino X 2,320 - X 1,998 - X 1,400. Categoría E: 75 neonatos con ictericia marcada registraron cifras de amonio plasmático (mcg/ml) (0-24; 24-48; 48-72 horas de vida)..

A Case of Rotor Syndrome / 영남의대학술지

Rotor syndrome is a rare disease of hereditary hyperbilirubinemia transmitted with autosomal recessive trait. In general, Rotor syndrome shows direct hyperbilirubinemia and there has been several reports since Sons's report in 1966, in Korea. A 34-year-old female was admitted with the chief complaint of intermittent icteric sclera for 24 years. There was no family history of jaundice. Rotor syndrome was diagnosed by oral cholecystogram, BSP retention test, 99mTc-DISIDA scan, liver biopsy and electron microscopy study of liver biopsy specimen. We report this case with brief review of the literature.

Síndrome de Rotor: apresentaçäo de um caso

Os autores apresentam um caso de síndrome de Rotor em paciente de 65 anos que desde os 10 anos apresenta icterícia assintomática, por hiperbilirrubinemia conjugada. A presença de colecistite calculosa e a operaçäo realizada mostraram a perfeita integridade do fígado e ductos biliares