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Abstract(s)
A drepanocitose é uma das hemoglobinopatias monogénicas mais comuns e severa no planeta, podendo colocar em risco a vida dos doentes. A presente monografia versa sobre a etiologia, fisiopatologia, diagnóstico e abordagens terapêuticas da drepanocitose, de modo a perceber a situação atual em Portugal, especialmente na área pediátrica.
A drepanocitose é caracterizada pela presença de hemoglobina S, resultante duma mutação do segundo nucleótido do sexto codão do gene HBB, conduzindo à substituição do aminoácido ácido glutâmico por valina na 6ª posição da cadeia de globina β.
A polimerização da hemoglobina S, que conduz ao aumento da rigidez das hemácias e à vaso-oclusão, é o cerne da fisiopatologia desta doença, estando associada a muitas complicações agudas e crónicas que requerem intervenção médica imediata.
Os dados epidemiológicos sobre esta hemoglobinopatia em Portugal estão desatualizados e não foi publicado nenhum estudo novo, dificultando a eficiência das medidas de intervenção estabelecidas pela normativa 08/DSMIA de 07/09/2004. Tendo em conta estas limitações e para resolvê-las, os peritos de Programa Nacional de Diagnóstico Precoce planeiam iniciar um estudo piloto de rastreio neonatal de hemoglobinopatias dentro dos próximos três anos.
A terapêutica clínica é essencialmente preventiva, estando recomendado o uso de hidroxiureia e de transfusão de sangue crónica, que, todavia, são subutilizadas. Apesar de ser segura a administração de hidroxiureia a partir de nove meses de idade, não existem ainda estudos de longo prazo que assegurem a inexistência de efeitos antineoplásicos indesejáveis.
A única terapêutica curativa disponível continua a ser o transplante de células hematopoiéticas. Todavia, esta abordagem tem uma fonte de dadores imunocompatíveis muito restrita e o recetor acarreta um risco de infertilidade. Assim, a terapia genética é uma nova área para a descoberta de uma cura universalmente aplicável.
A Sickle cell disease (SCD) is one of the most common and severe monogenic hemoglobinopathies in the world, putting the patient’s live at risk. The present monograph deals with the etiology, pathophysiology, diagnosis and therapeutic approaches to sickle cell disease, in order to understand the current situation in Portugal, especially in the pediatric area. SCD is characterized by the presence of hemoglobin S, that results from a mutation in the second nucleotide of the sixth codon of HBB gene, leading to substitution of amino acid glutamic acid to valine in the sixth position of β globin. Polymerization of hemoglobin S, which leads to the rigidity of the erythrocytes and vaso-occlusion, is at the heart of the pathophysiology of SCD, being associated with many acute and chronic complications that requires immediate medical intervention. The epidemiologic data about SCD in Portugal are outdated and no new study was published, making the intervention measures established by the 08/DMIA regulation of 07/09/2004 difficult. Given these limitations and to address them, the Programa Nacional de Diagnóstico Precoce experts plans to initiate a pilot study of neonatal screening for hemoglobinopathies within the next three years. The management is essentially preventive, recommending the use of hydroxyurea and chronic blood transfusion, however are underused. The administration of hydroxyurea Is considered safe in infants nine months or older, but it doesn’t have long-term studies to ensure that there are no undesirable antineoplasic effects. The only cure available remains the hematopoietic cell transplantation. However, this approach has a very restricted source of immunocompatible donors and the recipient carries a risk of infertility. Thus, gene therapy is a new area for the discovery of a universally applicable cure.
A Sickle cell disease (SCD) is one of the most common and severe monogenic hemoglobinopathies in the world, putting the patient’s live at risk. The present monograph deals with the etiology, pathophysiology, diagnosis and therapeutic approaches to sickle cell disease, in order to understand the current situation in Portugal, especially in the pediatric area. SCD is characterized by the presence of hemoglobin S, that results from a mutation in the second nucleotide of the sixth codon of HBB gene, leading to substitution of amino acid glutamic acid to valine in the sixth position of β globin. Polymerization of hemoglobin S, which leads to the rigidity of the erythrocytes and vaso-occlusion, is at the heart of the pathophysiology of SCD, being associated with many acute and chronic complications that requires immediate medical intervention. The epidemiologic data about SCD in Portugal are outdated and no new study was published, making the intervention measures established by the 08/DMIA regulation of 07/09/2004 difficult. Given these limitations and to address them, the Programa Nacional de Diagnóstico Precoce experts plans to initiate a pilot study of neonatal screening for hemoglobinopathies within the next three years. The management is essentially preventive, recommending the use of hydroxyurea and chronic blood transfusion, however are underused. The administration of hydroxyurea Is considered safe in infants nine months or older, but it doesn’t have long-term studies to ensure that there are no undesirable antineoplasic effects. The only cure available remains the hematopoietic cell transplantation. However, this approach has a very restricted source of immunocompatible donors and the recipient carries a risk of infertility. Thus, gene therapy is a new area for the discovery of a universally applicable cure.
Description
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2017
Keywords
Drepanocitose Pediatria Portugal Epidemiologia Hidroxiureia Transfusão de sangue Novos fármacos Transplantação Terapia genética Nucleases programáveis Mestrado Integrado - 2017