RESUMO
OBJECTIVE: To clarify the clinical, pathologic, and genetic features of neonatal Dubin-Johnson syndrome. STUDY DESIGN: Ten patients with neonatal Dubin-Johnson syndrome were recruited from 6 pediatric centers in Japan between September 2013 and October 2016. Clinical and laboratory course, macroscopic and microscopic liver findings, and molecular genetic findings concerning ATP-binding cassette subfamily C member 2 (ABCC2) were retrospectively and prospectively examined. RESULTS: All neonates exhibited cholestasis, evident as prolonged jaundice with or without acholic stools and elevations of serum direct bilirubin as well as γ-glutamyltransferase or total bile acids. Only 38% (3 of 8) of patients who underwent liver biopsy showed a grossly black liver or melanin-like pigment deposits in hepatocytes; their biopsies were performed in early infancy. Immunohistochemically, all liver specimens showed no expression of multidrug resistance-associated protein 2 but increased expression of the bile salt export pump protein. Homozygous or compound heterozygous pathogenic variants of ABCC2 were identified in all patients, representing 11 distinct pathogenic variants including 2 not previously reported. CONCLUSIONS: Immunohistochemical staining of the liver for multidrug resistance-associated protein 2 and molecular genetic analysis of ABCC2 are crucial for accurate diagnosis of neonatal Dubin-Johnson syndrome.
Assuntos
Icterícia Idiopática Crônica/diagnóstico , Icterícia Idiopática Crônica/genética , Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/metabolismo , Ácidos e Sais Biliares/metabolismo , Bilirrubina/metabolismo , China , Feminino , Hepatócitos/metabolismo , Humanos , Recém-Nascido , Doenças do Recém-Nascido , Japão , Icterícia , Icterícia Idiopática Crônica/patologia , Icterícia Idiopática Crônica/cirurgia , Fígado/metabolismo , Fígado/patologia , Masculino , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mutação , Estudos Prospectivos , Estudos RetrospectivosAssuntos
Bilirrubina/sangue , Colecistectomia/efeitos adversos , Colestase/etiologia , Icterícia Idiopática Crônica/diagnóstico , Icterícia Idiopática Crônica/etiologia , Adolescente , Biópsia , Diagnóstico Diferencial , Feminino , Humanos , Icterícia Idiopática Crônica/sangue , Icterícia Idiopática Crônica/patologia , Fígado/patologiaRESUMO
Se presentan 2 casos de síndrome de Dubin-Johnson, hermanos, un varón y una hembra, de 16 y 19 años, respectivamente. Ambos tuvieron el antecedente de ictericia recidivante sin diagnóstico definitivo. El varón fur remitido a nuestro centro por ictericia de 4 meses de evolución y la hembra con historia de ictericia en varias ocasiones durante los últimos 3 años, estudiada a partir del diagnóstico del hermano. En los 2 casos la laparoscopia y la biopsia hapática fueron diagnósticas y se obtuvieron muestras de tejido hepático para estudio ultraestructural. No existió asociación con litiasis vesicular. En el varón se observó además ceruloplasmina baja, aumento del cobre en tejido hepático fresco y de la excreción de cobre en orina, a pesar de que este síndrome no se asocia a otras hepatopatías. La ultraestructura del hígado mostró numerosos gránulos densos de pigmentos relacionados con los lisosomas y disminución o pérdida de vellosidades
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Biópsia , Fígado/ultraestrutura , Icterícia Idiopática Crônica/diagnóstico , Laparoscopia , Icterícia Idiopática Crônica/patologiaRESUMO
Relata-se um caso de síndrome de Dubin-Johnson com história de icterícia desde o nascimento, cujo diagnóstico foi confirmado pela presença do pigmento à microscopia hepática. Faz-se uma revisäo desta síndrome e procura-se compará-la a outras icterícias congênitas
Assuntos
Adulto , Humanos , Feminino , Icterícia Idiopática Crônica/patologia , Fígado/ultraestruturaRESUMO
Eight patients with Dubin-Johnson's syndrome have been reported. It appoints the greatest casuistry about the theme in our country. The coincidence covers all the aspects of the disease except by the fact that we emphasize, as a matter of interest, that we were able to visualize the gallblader and the biliary tract through oral cholecystography visualize the gallblader and the biliary tract through oral cholecystography or through intravenous cholangiography, in all the patients who have been studied. It doesn't agree with the class descriptions in which these exams have negative results. So we point out the possibility of this disease's existence in spite of the radiographic visulaization of biliary tract, particularly in those patients with moderated hepatic pigment-deposit. Refering to pathologic anathomy we remark the importance in the search of the pigment charactiristic of the Dublin-Johnson's syndrome in all the liver histopathologic exams. Besides, we consider it valuable to make the Fontana-Masson coloration in those patients who present negative pigment reaction to iron. The systematic examinations of the cytoplasmatic pigments will allow us to diagnose the disease even in the cases with minimum and latent characteristics.