RESUMO
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.
Assuntos
Humanos , Masculino , Doença de Gilbert , Personalidade , Transtornos da Personalidade , BilirrubinaRESUMO
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.
Assuntos
Doença de Gilbert , Bilirrubina , Humanos , Masculino , Personalidade , Transtornos da PersonalidadeRESUMO
Hyperbilirubinemia in patients with sickle cell anemia (SCA) as a result of enhanced erythrocyte destruction, lead to cholelithiasis development in a subset of patients. Evidence suggests that hyperbilirubinemia may be related to genetic variations, such as the UGT1A1 gene promoter polymorphism, which causes Gilbert syndrome (GS). Here, we aimed to determine the frequencies of UGT1A1 promoter alleles, alpha thalassemia, and ßS haplotypes and analyze their association with cholelithiasis and bilirubin levels. The UGT1A1 alleles, -3.7 kb alpha thalassemia deletion and ßS haplotypes were determined using DNA sequencing and PCR-based assays in 913 patients with SCA. The mean of total and unconjugated bilirubin and the frequency of cholelithiasis in GS patients were higher when compared to those without this condition, regardless of age (P < 0.05). Cumulative analysis demonstrated an early age-at-onset for cholelithiasis in GS genotypes (P < 0.05). Low fetal hemoglobin (HbF) levels and normal alpha thalassemia genotype were related to cholelithiasis development (P > 0.05). However, not cholelithiasis but total and unconjugated bilirubin levels were associated with ßS haplotype. These findings confirm in a large cohort that the UGT1A1 polymorphism influences cholelithiasis and hyperbilirubinemia in SCA. HbF and alpha thalassemia also appear as modulators for cholelithiasis risk.
Assuntos
Anemia Falciforme/sangue , Bilirrubina/sangue , Colelitíase/etiologia , Doença de Gilbert/sangue , Glucuronosiltransferase/fisiologia , Regiões Promotoras Genéticas/genética , Talassemia alfa/sangue , Adolescente , Adulto , Idoso , Alelos , Anemia Falciforme/complicações , Anemia Falciforme/enzimologia , Anemia Falciforme/genética , Criança , Pré-Escolar , Colelitíase/sangue , Colelitíase/genética , Feminino , Hemoglobina Fetal/análise , Genótipo , Doença de Gilbert/enzimologia , Doença de Gilbert/genética , Glucuronosiltransferase/genética , Haplótipos/genética , Hemólise , Humanos , Hiperbilirrubinemia/enzimologia , Hiperbilirrubinemia/etiologia , Hiperbilirrubinemia/genética , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Talassemia alfa/complicações , Talassemia alfa/enzimologia , Talassemia alfa/genéticaAssuntos
Colestase/diagnóstico , Doença de Gilbert/diagnóstico , Hiperbilirrubinemia/etiologia , Icterícia/etiologia , Cirrose Hepática/diagnóstico , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Bilirrubina/metabolismo , Colestase/complicações , Diagnóstico Diferencial , Doença de Gilbert/complicações , Humanos , Icterícia Obstrutiva/etiologia , Cirrose Hepática/complicações , Testes de Função Hepática , Hepatopatia Gordurosa não Alcoólica/complicaçõesRESUMO
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.
Assuntos
Humanos , Síndrome de Crigler-Najjar/diagnóstico , Doença de Gilbert/diagnóstico , Hiperbilirrubinemia Hereditária/diagnóstico , Icterícia Idiopática Crônica/diagnóstico , Síndrome de Crigler-Najjar/etiologia , Doença de Gilbert/etiologia , Hiperbilirrubinemia Hereditária/etiologia , Icterícia Idiopática Crônica/etiologiaRESUMO
Gilbert syndrome (GS) is a frequent benign clinical condition, marked by intermittent unconjugated hyperbilirubinemia, mostly due to the polymorphism uridine diphosphate-glucuronosyltransferase 1A1*28 (UGT1A1*28). Hyperbilirubinemia has been reported in a GS patient undergoing hepatitis C treatment, and other UGT isoforms polymorphisms have been linked to worse outcomes in viral hepatitis. Yet, little is known to GS contributions' to the liver disease scenario. Our aim was to assess UGT1A1 genotypes' frequency in chronic hepatitis C (CHC) patients and correlate with total bilirubin (TB). This is a case-control study in a large tertiary medical center. Cases were CHC patients confirmed by hepatitis C virus (HCV)-polymerase chain reaction. Exclusion criteria were hepatitis B virus or human immunodeficiency virus (HIV) coinfection. Control were healthy blood donors. UGT1A1 promoter region gene genotyping was performed, and bilirubin serum levels were available for HCV patients. Genotypes and alleles frequencies were similar in case (nâ=â585; Pâ=â0.101) and control groups (nâ=â313; Pâ=â0.795). Total bilirubin increase was noticed according to thymine-adenine repeats in genotypes (Pâ<â0.001), and the TB greater than 1âmg/dL group had more UGT1A1*28 subjects than in the group with TB values <1âmg/dL (18.3 vs 5.3; Pâ<â0.001). Bilirubin levels are linked to the studied polymorphisms, and this is the first time that these findings are reported in a chronic liver disease sample. Among patients with increased TB levels, the frequency of UGT1A1*28 is higher than those with normal TB. Personalized care should be considered to GS, regarding either abnormal bilirubin levels or drug metabolism.
Assuntos
Bilirrubina/sangue , Glucuronosiltransferase/genética , Hepatite C Crônica/sangue , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Doença de Gilbert/genética , Hepatite C Crônica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Adulto JovemRESUMO
El síndrome de Gilbert es una enfermedad benigna y hereditaria causada por la deficiencia relativa de la enzima glucuronil transferasa que es la causa más común de hiperbilirrubinemia congénita y que manifiesta clínicamente con ictericia, que puede aparecer antes, durante o después de la anestesia. Presentamos el manejo anestésico del caso de un paciente joven con síndrome de Gilbert que fue intervenido de amigdalectomía bajo anestesia general. Los fármacos y medicamentos anestésicos que utilizan esta enzima para su metabolismo o excreción deben ser evitados para minimizar el estrés hepático durante el período perioperatorio y permitir una conducción segura de la anestesia y evitar la icteria en estos pacientes.
Gilbert syndrome is a benign and hereditary disease caused by the relative deficiency of the enzyme glucuronyl transferase which is the most common cause of congenital hyperbilirubinemia and which manifests clinically with jaundice, which may appear before, during or after anesthesia. We present the anesthetic management of the case of a young patient with Gilbert's syndrome who underwent laparoscopic cholecystectomy under general anesthesia. Anesthetic drugs and drugs that use this enzyme for its metabolism or excretion should be avoided to minimize hepatic stress during the perioperative period and allow safe conduction of anesthesia and avoid jaundice in these patients.
Assuntos
Humanos , Masculino , Adolescente , Doença de Gilbert , Hiperbilirrubinemia , AnestesiaRESUMO
Gilbert's syndrome is a benign condition characterized by asymptomatic sporadic episodes of jaundice, due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation. Under certain physiologic or pathologic events bilirubin level rises but according to literature it does not reach out more than 3 mg/dl. We report 2 cases of Gilbert's syndrome, genetically tested, which presented with bilirubin levels above 6 mg/dl without any trigger or coexisting condition. In conclusion, bilirubin levels higher than 6 mg/dL in Gilbert syndrome are rare, hemolytic and other metabolism diseases must be ruled out, and genetic testing may be necessary in some cases.
Assuntos
Bilirrubina/sangue , Doença de Gilbert/sangue , Doença de Gilbert/diagnóstico , Hiperbilirrubinemia/sangue , Hiperbilirrubinemia/diagnóstico , Adolescente , Testes Genéticos , Doença de Gilbert/genética , Humanos , Hiperbilirrubinemia/genética , Masculino , Adulto JovemRESUMO
Pyrimidine-5'-nucleotidase type I (P5'NI) deficiency is an autosomal recessive condition that causes nonspherocytic hemolytic anemia, characterized by marked basophilic stippling and pyrimidine nucleotide accumulation in erythrocytes. We herein present two African descendant patients, father and daughter, with P5'N deficiency, both born from first cousins. Investigation of the promoter polymorphism of the uridine diphospho glucuronosyl transferase 1A (UGT1A) gene revealed that the father was homozygous for the allele (TA7) and the daughter heterozygous (TA6/TA7). P5'NI gene (NT5C3) gene sequencing revealed a further change in homozygosity at amino acid position 56 (p.R56G), located in a highly conserved region. Both patients developed gallstones; however the father, who had undergone surgery for the removal of stones, had extremely severe intrahepatic cholestasis and, liver biopsy revealed fibrosis and siderosis grade III, leading us to believe that the homozygosity of the UGT1A polymorphism was responsible for the more severe clinical features in the father. Moreover, our results show how the clinical expression of hemolytic anemia is influenced by epistatic factors and we describe a new mutation in the P5'N gene associated with enzyme deficiency, iron overload, and severe gallstone formation. To our knowledge, this is the first description of P5'N deficiency in South Americans.
Assuntos
5'-Nucleotidase/deficiência , Anemia Hemolítica Congênita/genética , Colestase/genética , Doença de Gilbert/genética , Glicoproteínas/genética , Sobrecarga de Ferro/genética , Cirrose Hepática/genética , 5'-Nucleotidase/genética , Adulto , Alelos , Anemia Hemolítica Congênita/complicações , Anemia Hemolítica Congênita/enzimologia , Anemia Hemolítica Congênita/patologia , Criança , Colestase/complicações , Colestase/enzimologia , Colestase/patologia , Consanguinidade , Epistasia Genética , Feminino , Doença de Gilbert/complicações , Doença de Gilbert/enzimologia , Doença de Gilbert/patologia , Heterozigoto , Homozigoto , Humanos , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/enzimologia , Sobrecarga de Ferro/patologia , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/enzimologia , Cirrose Hepática/patologia , Masculino , Regiões Promotoras Genéticas , Análise de Sequência de DNARESUMO
OBJECTIVE: To assess whether UGT1A1 promoter polymorphisms associated with Gilbert Syndrome (GS) occur with a greater frequency in neonates with severe hyperbilirubinemia. STUDY DESIGN: In a case-control study performed at a single hospital center in Italy, 70 case subjects with severe hyperbilirubinemia (defined as bilirubin level ≥20 mg/dL or 340 µmol/L) and 70 controls (bilirubin level <12 mg/dL or 210 µmol/L) were enrolled. Both case and control subjects were full term newborns. Polymerase chain reaction analysis on blood spot was performed to determine the frequency of UGTA1A1 promoter polymorphisms in cases and controls. RESULTS: No statistical difference in the prevalence of UGTA1A1 gene variants was found between cases and controls (P = 1). Thirteen infants homozygous for (TA)7 polymorphism associated with GS were in the case group (18.6%) and 14 in the control group (20.0%). A heterozygous group was also equally distributed between cases (44.3%) and controls (42.9%). No (TA)8 repeat was found in the 2 groups. CONCLUSIONS: In our study population, GS polymorphism alone does not appear to play a major role in severe neonatal hyperbilirubinemia in neonates without signs of hemolysis.