ABSTRACT
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.
Subject(s)
Humans , Crigler-Najjar Syndrome/diagnosis , Gilbert Disease/diagnosis , Hyperbilirubinemia, Hereditary/diagnosis , Jaundice, Chronic Idiopathic/diagnosis , Crigler-Najjar Syndrome/etiology , Gilbert Disease/etiology , Hyperbilirubinemia, Hereditary/etiology , Jaundice, Chronic Idiopathic/etiologyABSTRACT
La hiperbilirrubinemia no conjugada es una condición producida por una alteración en el proceso de conjugación y excreción de la bilirrubina. La glucoronosiltransferasa uridin difosfato es la responsable en la conjugación de la bilirrubina, es codificada por el gen de UGT1A1 localizado en el brazo q del cromosoma 2 locus 37.1. La variación genética del UGT1A1 puede producir diferentes fenotipos desde el más severo llamado Sindrome Crigler-Najjar Tipo I y II, pasando por el Sindrome de Gilbert; hasta una hiperbilirrubinemia transitoria neonatal o síndrome LUCEY-DRISCOLL (HBLRTFN) fenotipo OMIM 237900 con producción de kernicterus y parálisis cerebral pero con resolución espontánea, todos ellos de herencia autosómica recesiva causada por mutación homocigota o heterocigota en el gen UGT1A1. En este reporte se presenta un caso en un recién nacido que a los 7 días presenta hiperbilirrubinemia severa con kernicterus, y la prueba genética muestra mutación heterocigota del *28 del gen UGT1A1
Unconjugated hyperbilirubinemia is produced by alteration in conjugation and excretion process of bilirubin. Glucoronosiltransferasa Uridine diphosphate enzyme is involved in bilirubin conjugation. Is encoded by the UGT1A1 gene located in chromosome 2q locus 37.1. UGT1A1 genetic variation can produce different phenotypes Crigler-Najjar Syndrome Type I and II, Gilbert Syndrome, and hyperbilirubinemia transited familial LUCEY-DRISCOLL (HBLRTFN) syndrome with kernicterus production but with spontaneous resolution, all autosomal recessive. We present here a case of newborn 7 days old with severe hyperbilirubinemia , kernicterus, and genetic testing shows heterozygous mutation of the UGT1A1 * 28 gene
Subject(s)
Humans , Sexual VulnerabilityABSTRACT
Objetivos: Os autores descrevem um caso de síndrome de Crigler-Najjar tipo 2, um distúrbio hereditário do metabolismo da bilirrubina, resultante de um déficit parcial da enzima uridino-difosfo-glicuronil-transferase (UDPG T).Descrição do caso: Uma lactente de etnia asiática foi internada com cinco semanas de vida por icterícia persistente desde o nascimento, com relato materno de agravamento progressivo. Ao exame objetivo apresentava-se ativa, reativa, ictérica e com ligeira hipotonia axial. A investigação complementar mostrou um aumento da bilirrubina total (32,94 mg/dL), com bilirrubina direta de 0,94 mg/dL, e o estudo molecular revelou duas mutações em heterozigotia no gene UGT1A1 (c.211G>A e c.1456T>G), resultado compatível com síndrome de Crigler-Najjar tipo 2. Foi submetida a fototerapia intensiva em associação com quelante dos ácidos biliares, com resposta parcial. Após conhecimento do resultado do estudo molecular iniciou fenobarbital, ocorrendo normalização dos valores de bilirrubina após duas semanas.Conclusões: A síndrome de Crigler-Najjar tipo 2, embora fenotipicamente semelhante ao tipo 1, tem tratamento e prognóstico diferentes. Neste caso, a apresentação neonatal precoce e os valores de bilirrubina muito elevados, que não cediam totalmente à fototerapia intensiva, levaram inicialmente à suspeita de síndrome de Crigler-Najjar tipo 1, que é a forma mais grave. Os autores pretendem com este caso alertar para uma causa rara de icterícia, que não teve a apresentação típica.
Aims: The authors describe a case of Crigler-Najjar syndrome type 2, an inherited disorder of bilirubin metabolism resulting from a partial deficit of the enzyme uridine- diphospho-glucuronyl transferase (UDPG-T).Case description: A female infant of Asian ethnicity was admitted with five weeks of age by persistent jaundice since birth, with maternal report of progressive worsening. Upon physical examination the patient was active, reactive, and jaundiced, with mild axial hypotonia. Complementary examination showed increase in total bilirubin (32.94 mg/dL), with direct bilirubin of 0.94 mg/dL, and molecular study revealed two heterozygous mutations in the UGT1A1 gene (c.211G>A and c.1456T>G), consistent with Crigler-Najjar syndrome type 2. She was submitted to intensive phototherapy in combination with bile acid chelator, with a partial response. After reading the results of molecular studies, phenobarbital was started, leading to normal levels of bilirubin in two weeks.Conclusions: Crigler-Najjar syndrome type 2, although phenotypically similar to type 1, has different prognosis and treatment. In this case, early neonatal presentation and very high bilirubin values not fully yielded to intensive phototherapy, initially raised the suspicion of Crigler-Najjar syndrome type 1, which is the most severe form of the syndrome. With this report, the authors wish to draw attention to a rare cause of jaundice, which did not have its typical course.