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A distrofia muscular de Duchenne é uma doença genética recessiva ligada ao cromossoma X. Esta é a forma mais comum de distrofia muscular em crianças, afetando 1 em cada 3500 recém-nascidos do sexo masculino (1). Juntamente com a forma menos agressiva de distrofia muscular (distrofia de Becker), estas constituem o segundo grupo de doenças hereditárias mais comuns em humanos (2). Geneticamente é um defeito na codificação de uma proteína do músculo esquelético: a distrofina. O gene que a codifica é o maior no genoma humano (3). Este facto permite que ocorram mais facilmente tanto mutações novas como erros de síntese da proteína nalguma etapa. Clinicamente apresenta-se sobretudo por um enfraquecimento progressivo dos músculos levando a anormalidades da marcha e quedas frequentes entre os 3 e os 5 anos. Ocorre também uma cifoscoliose que vai avançando em termos de gravidade. Mais ainda, os indivíduos afetados costumam deixar de andar pelos 12 anos e têm falência respiratória na segunda ou terceira décadas de vida (4).
Desde que a doença foi pela primeira vez descrita em 1868 por Guillaume Duchenne (5) que se têm estudado várias estratégias para mitigar os efeitos ou mesmo tentar curar o problema na sua génese. Contudo ainda não se conseguiu encontrar uma terapia completamente eficaz e curativa no combate desta doença. Estão em curso vários ensaios clínicos para o efeito. Os objetivos deste trabalho serão então analisar de uma forma breve a distrofia de Duchenne abordando-a sob o ponto de vista da etiologia, fisiopatologia, genética, manifestações clínicas e diagnóstico bem como rever as estratégias terapêuticas atualmente existentes e em estudo, dando uma perspetiva de futuro.
A pesquisa bibliográfica obteve-se a partir das bases de dados PubMed e Medscape, e foram ainda consultados alguns livros de referência sobre o assunto em apreço. A pesquisa foi realizada em Inglês.
Depois de uma investigação alargada, foi possível concluir que ainda não existe uma terapêutica completamente acessível e eficaz para esta doença. Até hoje apenas uma classe de fármacos conseguiu resultados no atraso da progressão da doença, aumentando a força e função dos músculos esqueléticos: os glicocorticóides (6).
O futuro é muito promissor no campo da genética, principalmente com o skipping de exões, ao ser possível que o paciente expresse distrofina parcialmente funcional que reduzirá o impacto da doença.
The Duchenne muscular dystrophy is a genetic X-linked recessive disease. This is the most common form of muscular dystrophy in children, affecting 1 in 3500 newborn males (1). Together with the less aggressive form of muscular dystrophy (Becker’s dystrophy), these are the second most common hereditary disorders in humans (2). Genetically it is a defect in a skeletal muscle protein encoding: dystrophin. The gene encoding it is the largest in the human genome (3). This fact allows it to occur both new mutations as well as errors in the protein synthesis at some level. Clinically it mainly presents as a progressive weakening of the muscles leading to gait abnormalities and frequent falls between the ages of 5 and 7 years. Moreover, affected individuals often stop walking at the age of 12 years and have respiratory failure in the second or third decade of life (4). Since the disease was first described in 1868 by Guillaume Duchenne (5), it has been studied many strategies to mitigate the effects or even try to cure the problem in its genesis. But still one could not find a completely effective and curative therapy to fight this disease. There are several ongoing clinical trials for this purpose. The objectives of this study will then be to briefly examine the Duchenne’s dystrophy, approaching it in terms of etiology, pathophysiology, genetics, clinical features and diagnosis as well as review the therapeutic strategies that currently exist, giving a perspective of the future. The literature research was obtained from PubMed and Medscape databases and were also consulted some reference books on the subject at hand. The research was conducted in English. After an extensive investigation, it was possible to conclude that there is still no fully accessible effective therapy for this disease. Until now only one class of drugs could result in the delay of progression of the disease, increasing the strength and function of skeletal muscle: glucocorticoids (6). The future is very promising in the field of genetics, especially with exon skipping, that makes possible for the patient to express partially functional dystrophin which will reduce the impact of the disease.
The Duchenne muscular dystrophy is a genetic X-linked recessive disease. This is the most common form of muscular dystrophy in children, affecting 1 in 3500 newborn males (1). Together with the less aggressive form of muscular dystrophy (Becker’s dystrophy), these are the second most common hereditary disorders in humans (2). Genetically it is a defect in a skeletal muscle protein encoding: dystrophin. The gene encoding it is the largest in the human genome (3). This fact allows it to occur both new mutations as well as errors in the protein synthesis at some level. Clinically it mainly presents as a progressive weakening of the muscles leading to gait abnormalities and frequent falls between the ages of 5 and 7 years. Moreover, affected individuals often stop walking at the age of 12 years and have respiratory failure in the second or third decade of life (4). Since the disease was first described in 1868 by Guillaume Duchenne (5), it has been studied many strategies to mitigate the effects or even try to cure the problem in its genesis. But still one could not find a completely effective and curative therapy to fight this disease. There are several ongoing clinical trials for this purpose. The objectives of this study will then be to briefly examine the Duchenne’s dystrophy, approaching it in terms of etiology, pathophysiology, genetics, clinical features and diagnosis as well as review the therapeutic strategies that currently exist, giving a perspective of the future. The literature research was obtained from PubMed and Medscape databases and were also consulted some reference books on the subject at hand. The research was conducted in English. After an extensive investigation, it was possible to conclude that there is still no fully accessible effective therapy for this disease. Until now only one class of drugs could result in the delay of progression of the disease, increasing the strength and function of skeletal muscle: glucocorticoids (6). The future is very promising in the field of genetics, especially with exon skipping, that makes possible for the patient to express partially functional dystrophin which will reduce the impact of the disease.
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Associada A: Etiologia Distrofia de Duchenne Fisiopatologia Genética Tratamento