RESUMO
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
OBJECTIVE: Prolonged neonatal jaundice, beyond day 14 of life, is very common and of concern to the clinician. The aim of this study was to investigate whether a genetic mutation in the bilirubin UGT1A1 gene, which has been associated with Gilbert's syndrome in adults, is a contributory factor in prolonged neonatal jaundice. STUDY DESIGN: Blood was collected from 85 term newborns with unexplained hyperbilirubinemia, and DNA was prepared. The neonates were divided into 6 groups depending on whether they were breast-fed or bottle-fed and whether they had acute, prolonged, or very prolonged jaundice. UGT1A1 TATA promoter genotyping (DNA test for Gilbert's syndrome) was performed on all samples, and analysis of the entire UGT1A1 coding sequence was performed in a representative sample (11 of 26) of very prolonged cases. RESULTS: In addition to the known common UGT1A1 TATA alleles (TA6 and TA7), a novel TATA allele (TA5) in a neonate with very prolonged jaundice was identified. Statistical analysis of the TATA genotype distributions within the group of breast-fed neonates revealed significant differences among the acute, prolonged, and very prolonged subgroups (.05 > P >.01): the incidence of familial hyperbilirubinemia genotypes (7/7 and 5/7) is 5 times greater in very prolonged cases (31%) relative to acute cases (6%). Neonates with prolonged jaundice from family pedigrees were observed to demonstrate the Gilbert's phenotype as children or young adults. CONCLUSIONS: A genetic predisposition to develop prolonged neonatal hyperbilirubinemia in breast-fed infants is associated with TATA box polymorphism of the UGT1A1 gene and will be recognized as Gilbert's syndrome in adulthood.
Assuntos
Aleitamento Materno/efeitos adversos , Doença de Gilbert/genética , Glucuronosiltransferase/genética , Hiperbilirrubinemia Hereditária/genética , Adolescente , Adulto , Alimentação com Mamadeira , Criança , Feminino , Genótipo , Doença de Gilbert/complicações , Humanos , Hiperbilirrubinemia Hereditária/etiologia , Recém-Nascido , Masculino , Linhagem , Reação em Cadeia da Polimerase , Polimorfismo Genético , Análise de Sequência , TATA Box/genéticaRESUMO
O autor apresenta as observaçÆes de seis pacientes portadores da Síndrome de Gilbert, diagnosticados e acompanhados em sua clínica particular, nos últimos dois anos, tecendo comentários sobre a conceituaçäo de referida síndrome, sua provável etiopatogenia, benignidade do quadro clínico presente e métodos semiológicos utilizados para seu diagnóstico, compreendendo anammese, exame físico, provas laboratoriais, biópsia hepática com exame histopatológico de fragmentos do fígado, dieta baixa em calorias, ou em lipídios, e testes de contra-prova através do uso oral do fenobarbital. Pôde comprovar, no estudo de seus casos, o aumento discreto ou moderado da bilirrubinemia às custas da fraçäo indireta ou näo conjugada; a normalidade das provas hepáticas realizadas; o aparecimento ou desaparecimento das crises de icterícia, pelo menos em alguns casos, após reduçäo do número de calorias e (ou) prática exagerada de exercícios físicos; a ausência de qualquer tipo de anormalidade no exame histopatológico de fragmentos de fígado, obtidos por biópsia hepática, no único caso em que foi utilizado; e, finalmente, a contraprova da baixa da bilirrubinemia mediante o emprego oral de fenobarbital