Associations between Gilbert's syndrome and personality characteristics

Abstract Objective Gilbert's syndrome (GS) is a benign genetic disorder that is characterized by intermittent mild jaundice in which the liver doesn't process bilirubin properly. The aim of this study was to determine whether GS patients have a different personality structure and if there are associations between properties of temperament and character and total bilirubin levels. Methods A total of 1665 young male individuals aged from 19 to 30 who were admitted for occupational examinations were included in this study. Careful patient history was taken, a detailed physical examination was conducted, and hematologic and biochemical tests and abdominal ultrasonography were performed. The Turkish version of the Temperament and Character Inventory (TCI) was administered to all participants. 81 patients diagnosed with GS and 150 randomly chosen healthy individuals (control group) were investigated with comparison and correlation analyses. Results GS patients had higher scores than healthy controls for disorderliness (NS4) (p = 0.018), sentimentality (RD1) (p = 0.042), and fatigability (HA4) (p = 0.03). Moreover, Gilbert syndrome patients scored lower than controls for empathy (C2) (p = 0.041) and transpersonal identification (ST2) (p = 0.044). Bilirubin levels were positively associated with disorderliness (NS4) (r = 0.141, p = 0.032) and fatigability (HA4) (r = 0.14, p = 0.033). Conclusions GS patients may have some different personality characteristics from healthy individuals. This study is an initial exploration of the personality structure of GS patients and the findings should be interpreted with caution. Further prospective studies are needed to identify the relationship between Gilbert disease and personality characteristics.

Gilbert syndrome in a young boy with thalassemia trait: a rare association

Gilbert syndrome (GS) is a mild benign disease characterized by asymptomatic unconjugated hyperbilirubinemia in absence of liver disease or hemolysis. This is the most common disorder associated with bilirubin metabolism with autosomal recessive inheritance. It usually precipitates during episodes of dehydration, fasting or stress like intercurrent illnesses. Here, we are reporting a case of Gilbert syndrome in 12 yrs old boy with thalassemia trait who presented with history of persistent jaundice for last 10 months. He had disproportionately higher concentration of unconjugated bilirubin which cannot be attributed to either disorder alone. Authors considered the possibility of Gilbert syndrome after ruling out hemolytic anemia. Though genetic testing is considered to be gold standard for diagnosis of Gilbert syndrome but availability is an issue. Calorie restriction test and nicotinic acid provocation test has been used to confirm GS too. Rifampicin test, another simple test which has been described in literature though not widely used in diagnosis. It has high sensitivity and specificity too. Authors had performed rifampicin test in our index case to confirm the diagnosis of GS. Here, authors wish to highlight the patients with both GS and thalassemia trait has higher bilirubin concentrations and is more likely to be icteric than either defect alone.

Apatinib as Salvage Therapy for Heavily Pretreated SCLC / 中国肺癌杂志

Small cell lung cancer (SCLC) was highly malignant and lack effective treatment after the failure of radiotherapy and chemotherapy. Antiangiogenic therapy had shown a certain effect in advanced SCLC. Apatinib, a new potent oral small-molecule tyrosine kinase inhibitor targeting the intracellular domain of vascular endothelial growth factor receptor 2 (VEGFR-2), showed the effect of anti-angiogenesis. However, the efficacy in SCLC was rarely reported. We reported 1 case of advanced SCLC with Gilbert syndrome, the patient received Apatinib after the failure of 4 lines of chemotherapy, and achieved a partial response according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 standard after one month. The progression-free survival (PFS) was 5 months. Apatinib was well tolerated except recurrent grade 3 hyperbilirubinemia because of the metabolic disorder of Bilirubin. Salvage treatment with Apatinib for advanced SCLC deserved further exploration.
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Analysis of genetic mutation of UGT1A1 * 28 and UGT1A1 * 6 in renal transplant patients with unconjugated hyperbilirubinemia / 中华器官移植杂志

Objective To explore the clinical significance and gene mutation profiles of renal transplant patients with unconjugated hyperbilirubinemia (Gilbert's syndrome).Methods Genomic DNA was extracted from peripheral blood samples of 8 renal transplant patients with Gilbert'S syndrome.UGT1A1 * 6 and UGT1A1 * 28 genotypes were identified through digital fluorescence molecular hybridization and DNA sequencing.Results There are 2 cases of UGT1A1 * 28 heterozygous mutant,3 cases of UGT1A1 * 6 homozygous mutant,2 case of UGT1A1 * 6 heterozygous mutant,1 case of UGT1A1 * 28 heterozygous mutant combined with UGT1A1 * 6 heterozygous mutant.Conclusion There is a higher heterozygous or homozygous gene mutation rate of UGT1A1 * 6 and UGT1A1 * 28 in renal transplant patients with Gilbert's syndrome.Genetic mutation of UGT1A1 * 6 and UGT1A1 * 28 may be the reason of Gilbert's syndrome after renal transplant.

Pruebas de laboratorio en el síndrome de Gilbert consecutivo a hepatitis / Laboratory tests in Gilbert's syndrome subsequent to hepatitis

Se efectuó un estudio descriptivo y transversal de 40 pacientes con síndrome de Gilbert consecutivo a hepatitis viral aguda, admitidos en el Servicio de Medicina Interna del Hospital Provincial Docente Clinicoquirúrgico Saturnino Lora Torres de Santiago de Cuba o en la consulta especializada de Hepatología del Policlínico de Especialidades de esta institución, desde junio del 2011 hasta igual mes del 2012, a fin de determinar las características clínico humorales y la respuesta al tratamiento médico en estos. En la casuística se evaluaron las medias, medianas y desviaciones estándares, y entre los resultados se observaron una mayor representación de los hombres menores de 36 años (90,0 por ciento del total), así como un predominio de las manifestaciones de somnolencia, seguida de la astenia, ictericia leve y ausencia de síntomas; asimismo, se confirmó la elevación de la bilirrubina indirecta y su posterior disminución al aplicar la terapia con un inductor enzimático, en este caso el fenobarbital, con el cual se obtuvo, finalmente, mejoría clínica y humoral de los afectados

A descriptive and cross-sectional study was carried out in 40 patients with Gilbert's syndrome subsequent to viral hepatitis, admitted to the Internal Medicine Department of Saturnino Lora Torres Provincial Clinical Surgical Teaching Hospital of Santiago de Cuba or to the specialized hepatology service of the Polyclinic of Specialties in this institution, from June 2011 to the same month of 2012, to determine the clinical and humoral characteristics and the response to medical treatment in them. Means, medians and standard deviations were evaluated in the case material, and among the results was a greater representation of males younger than 36 years (90.0 percent of the total), and a prevalence of manifestations of drowsiness, followed by sleepiness, mild jaundice and absence of symptoms was observed. Also, the elevation of indirect bilirrubin and its subsequent reduction when applying therapy with an enzyme inducer, phenobarbital in this case, were confirmed, eventually obtaining clinical and humoral improvement of patients

Wayward effect of polymorphism (TA)8 in the promoter region of UGT1A1 gene in a Mexican family / Efecto caprichoso del polimorfismo (TA)8 en la región del promotor del gene UGT1A1 en una familia mexicana

Gilbert syndrome (GS) is a hereditary relatively common benign unconjugated hyperbilirubinaemia. The promoter region of uridine diphosphate glycosyltransferase 1 (UGT1A1) gene contains a normal A(TA)6 TAA element; variations in this motif (A(TA)7/8 TAA) are generally associated with this disorder. This is a report of the varied effects of GS in a Mexican Mestizo family with a non-common (TA)8 repeat in this population. T he proposita and her mother showed (TA)7 /(TA)8 genotype, while her father and sister were (TA)6 /(TA)7 , but only the proposita showed clinical manifestations. This report supports that the (TA)7 and (TA)8 are necessary, but not enough to explain the features of GS. There are probably additional genetic variations ie, the presence of "modifier" genes or one can speculate that an oligogenetic trait can contribute to the expression of the final phenotype.

El síndrome de Gilberto (SG) es un hiperbilirubinemia no conjugada, benigna, relativamente común y hereditaria. La región promotora del gen (UGT1A1) de la uridina difosfato glicosiltransferasa 1, contiene un elemento normal A (TA)6 TAA. Las variaciones en este motivo (A (TA)7/8 TAA) se encuentran por lo general asociadas con este desorden. Éste es un reporte de los variados efectos del SG en una familia mestiza mexicana con una repetición (TA)8 no común en esta población. La probando y su madre mostraron el genotipo (TA)7 /(TA)7 , mientras su padre y hermana eran (TA)6 /(TA)7 , pero sólo la probando mostró manifestaciones clínicas. Este informe sostiene que el (TA)7 y (TA)8 son necesarios, pero no suficientes para explicar los rasgos del SG. Probablemente hay variaciones genéticas adicionales, es decir, la presencia de genes "modificadores", o se puede especular que un rasgo oligogenético puede contribuir a la expresión del fenotipo final.

Severe Jaundice in Two Children with Kawasaki Disease: A Possible Association with Gilbert Syndrome

Kawasaki disease is a systemic vasculitis, mainly encountered in children. It may affect any organ. Acute cholestasis and severe obstructive jaundice is an atypical manifestation of the disease. We herein present two children with Kawasaki disease and severe direct hypebilibirunemia who also were homozygous and heterozygous respectively for the (TA)7 promoter polymorphism of Gilbert syndrome. Intravenous immunoglobulin was administered to both patients at the acute phase of the disease and the fever remitted within 24 hr following the immunoglobulin administration. Furthermore oral aspirin at a dose of 80-100 mg/kg/24 hr was also given. The first child did not develop any coronary ectasia or aneurysm, whereas dilation of the right coronary artery was identified in the second child, one month after the disease onset. We discuss the possible contribution of Gilbert syndrome to the development of jaundice in our patients.

A Case of Gilbert's Syndrome with Severe Neonatal Hyperbilirubinemia

Gilbert's syndrome is caused by a reduction in the activity of uridine diphosphate glucuronosyltransferase (UGT) and induces chronic, non-hemolytic unconjugated hyperbilirubinemia. It has been suggested that 3-10% of the population has Gilbert's syndrome. Commonly, Gilbert's syndrome causes mild symptoms. However, a case of Gilbert's syndrome with severe neonatal hyperbilirubinemia is presented here. The patient developed jaundice three days after birth. Five days after birth, the patient's total serum bilirubin level was 34 mg/dL. The patient received intensive phototherapy and was given oral phenobarbital. Hemolytic hyperbilirubinemia was excluded on the basis of laboratory tests. Heterozygote polymorphisms of the promoter region (-3279T>G) and exon 1 (211G>A) were found in UGT1A1 gene. After discharge, the patient did not require any further treatment. This is the first case of proven Gilbert's syndrome with severe neonatal hyperbilirubinemia in Korea.

A Case of Gilbert's Syndrome with Severe Neonatal Hyperbilirubinemia

Gilbert's syndrome is caused by a reduction in the activity of uridine diphosphate glucuronosyltransferase (UGT) and induces chronic, non-hemolytic unconjugated hyperbilirubinemia. It has been suggested that 3-10% of the population has Gilbert's syndrome. Commonly, Gilbert's syndrome causes mild symptoms. However, a case of Gilbert's syndrome with severe neonatal hyperbilirubinemia is presented here. The patient developed jaundice three days after birth. Five days after birth, the patient's total serum bilirubin level was 34 mg/dL. The patient received intensive phototherapy and was given oral phenobarbital. Hemolytic hyperbilirubinemia was excluded on the basis of laboratory tests. Heterozygote polymorphisms of the promoter region (-3279T>G) and exon 1 (211G>A) were found in UGT1A1 gene. After discharge, the patient did not require any further treatment. This is the first case of proven Gilbert's syndrome with severe neonatal hyperbilirubinemia in Korea.

A case of concomitant Gilbert's syndrome and hereditary spherocytosis / 대한간학회지

We describe moderate hyperbilirubinemia in a 28-year-old man who suffered from gallstones and splenomegaly, with combined disorders of hereditary spherocytosis (HS) and Gilbert's syndrome (GS). Since it is difficult to diagnose HS in the absence of signs of anemia, we evaluated both the genetic mutation in the UGT1A1 gene and abnormalities in the erythrocyte membrane protein; the former was heterozygous for a UGT1A1 allele with three mutations and the latter was partially deficient in ankyrin expression. This is the first report of the concomitance of HS and GS with three heterozygous mutations [T-3279G, A (TA)7TAA, and G211A] in the UGT1A1 gene.

Gilbert's syndrome and molecular genetics basis / 国际儿科学杂志

Gilbert's syndrome is a congenital,nonhemolytic,unconjugated hyperbilirubinemia.The intermittent mild jaundice is its clinical characteristic.The pathogenesis of the disease is the gene mutation of the isoenzyme which encoding the UDP-glucuronosyltransferase (UGT1A1).The gene mutation can affect glucuronic acidation of drugs.Therapeutic dose can cause unexpected toxicity.It is very important to detect the gene mutation of UGT1A1 for diagnosis,treatment and genetic counseling of Gilbert's syndrome.

A Case of Congenital Hemolytic Anemia of Unknown Cause Combined with Gilbert's Syndrome

Congenital hemolytic anemia is mainly developed due to intrinsic defects of erythrocytes, but in some cases the cause of hemolytic anemia is unclear. Gilbert's syndrome shows mild, chronic unconjugated hyperbilirubinemia that is due to reduced UDP glucuronosyltransferase (UGT-1A1) activity and this develops because of UGT-1A1 gene mutation. We report here on a case of severe hyperbilirubinemia in a 17-year-old male who was diagnosed with congenital hemolytic anemia of an unknown cause combined with Gilbert's syndrome.

Isolated Unconjugated Hyperbilirubinemia after Liver Transplantation

PURPOSE: In our experience, post-LT persistent isolated unconjugated hyperbilirubinemia (IUH) has been frequently observed even after liver transplantation (LT) from normal donors. The present study was performed to evaluate the incidence and clinical significance of post-LT IUH. METHODS: Eighty-five patients were enrolled, and they had undergone adult-to-adult living donor LT between Jan 1999 and Jun 2003 and they had been followed-up for more than 2 years. Persistent post-LT IUH was defined as the case that showed repeated IUH 3 times or more per year. We excluded those cases that had other liver function abnormality, biliary complication, active infection or hemolysis. The donor's condition and the long-term prognosis of the post-LT IUH patients were investigated. RESULTS: Sixteen patients (18.8%) showed post-LT IUH. Seven of them underwent LT from donors who had IUH preoperatively. Nine (10.6%) of them, however, underwent LT from normal donors, that is, there was newly developed IUH postoperatively. There was no clinical factor associated with post-LT IUH for those nine patients, yet they developed no graft failure and major complications. A gradual increasing tendency of the bilirubin level during follow-up duration was observed for 3 of these 9 patients. CONCLUSION: Although about 10% patients developed post-LT IUH from normal donors, they all showed a good prognosis. Therefore, post-LT IUH was likely to be benign. However, close observation may be required because a gradual increasing tendency of bilirubin level was observed in some patients.