| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 803.72 KB | Adobe PDF |
Authors
Advisor(s)
Abstract(s)
A colestase neonatal é uma das formas mais comuns de doença hepática na
infância e afeta cerca de 1:2500 recém-nascidos. A etiologia divide-se entre intra- e extrahepáticas e dentro do primeiro grupo incluem-se as causas genéticas, que resultam em
distúrbios no metabolismo, defeitos da embriogénese ou da morfologia biliar, entre
outros. Estas doenças associam-se a um impacto significativo na morbimortalidade e no
número de transplantes hepáticos em idade pediátrica. A sua identificação precoce é de
extrema importância, uma vez que pode permitir uma janela de oportunidade para
intervir de maneira a obter um melhor prognóstico.
O objetivo desta Dissertação foi apresentar uma revisão atualizada sobre as causas
genéticas de doença colestática neonatal, em particular os achados clínicos, métodos de
diagnóstico, abordagens terapêuticas e aspetos do prognóstico. Para tal, realizou-se uma
pesquisa na PubMed e ainda a consulta de alguns livros relevantes da área.
Nesta Revisão constatou-se um grande avanço nos meios de diagnóstico com o
desenvolvimento do Next-generation sequencing, que permitem a confirmação do
diagnóstico, quando os estudos bioquímicos e histopatológicos não são suficientes. Além
disso, verificou-se que há cada vez mais conhecimento dos mecanismos fisiopatológicos da
colestase neonatal, o que tem permitido a identificação de novos alvos terapêuticos que
poderão melhorar o tratamento e qualidade de vida destas crianças.
Neonatal cholestasis is one of the most common forms of childhood liver disease and affects approximately 1:2500 newborns. The etiology is classified into intra- or extrahepatic. The first group includes genetic causes, for example, metabolic disorders, defective embryogenesis, or biliary morphology, among others. These diseases are associated with a significant impact on morbimortality and the number of pediatric liver transplants. Its early identification is extremely important, as it may allow a window of opportunity to intervene to obtain a better prognosis. The goal of this Dissertation was to present an up-to-date review of genetic causes of neonatal cholestatic disease, in particular the clinical findings, diagnostic methods, therapeutic approaches, and aspects of prognosis. For this, a PubMed search was conducted, but also some relevant books were consulted. In this Review, great progress was found in the diagnostic methods with the development of next-generation sequencing, which confirms the diagnosis, when biochemical and histopathological studies are insufficient. In addition, it was verified that there is increasing knowledge of the pathophysiological mechanisms of neonatal cholestasis, which has allowed the identification of new therapeutic targets that could improve the treatment and quality of life of these newborns.
Neonatal cholestasis is one of the most common forms of childhood liver disease and affects approximately 1:2500 newborns. The etiology is classified into intra- or extrahepatic. The first group includes genetic causes, for example, metabolic disorders, defective embryogenesis, or biliary morphology, among others. These diseases are associated with a significant impact on morbimortality and the number of pediatric liver transplants. Its early identification is extremely important, as it may allow a window of opportunity to intervene to obtain a better prognosis. The goal of this Dissertation was to present an up-to-date review of genetic causes of neonatal cholestatic disease, in particular the clinical findings, diagnostic methods, therapeutic approaches, and aspects of prognosis. For this, a PubMed search was conducted, but also some relevant books were consulted. In this Review, great progress was found in the diagnostic methods with the development of next-generation sequencing, which confirms the diagnosis, when biochemical and histopathological studies are insufficient. In addition, it was verified that there is increasing knowledge of the pathophysiological mechanisms of neonatal cholestasis, which has allowed the identification of new therapeutic targets that could improve the treatment and quality of life of these newborns.
Description
Keywords
Colestase Neonatal Diagnóstico Genética Next-Generation Sequencing