Familial Amyloid Polyneuropathy: A Proposal for an Epidemiological Study Through the Creation of a Virtual Platform

Amyloidosis are characterized by mutations in the gene coding for transthyretin (TTR), located on chromosome 18. TTR is a set of four 127-aminoacid polypeptides structured as homotetrameric protein of 56 kDa with a secondary ß sheet structure. It plays the role of thyroxin (T4) carrier, and has a bindingdomain for retinol (vitamin A). It is synthesized in the liver, although a small quantity is also produced by the choroid plexus, and retinal cells. Mutations of this gene result in loss of tetramer stability. Insoluble amyloid fibrils (AF) are formed and deposited in tissues and organs. The abnormal aggregation ofTTR protein trigger several syndromes, such as familial amyloid polyneuropathy (FAP-TTR), cardiomyopathies (CMP), and senile systemic amyloidosis (SSA). It is estimated there are 5,000 to 10,000 cases of FAP-TTR globally. Objective: The study intends to develop an online platform for the diagnosis of FAP-TTR. The aim is to facilitate the diagnosis process and promote a tool for epidemiological study.Methods: The project was based on a literature review featuring clinical and epidemiological evidence for the development of a practical platform (applied research). Results: It was elaborated a platform containing a questionnaireto allow a more dynamic, cheaper, and efficient operation, mediated by a better characterization of the disease to enable its early diagnosis. Conclusion: The platform might become a valuable resource for the characterization, diagnosis, and future epidemiological study of FAP-TTR

Polineuropatia amiloidótica familiar: uma proposta de estudo epidemiológico por meio da criação de uma plataforma virtual

As amiloidoses são doenças que se caracterizam por mutações no gene codificante da transtirretina (TTR), localizado no cromossomo 18. A proteína TTR, antes designada como préalbumina, compõe-se de uma corrente de polipeptídios de 127 resíduos de aminoácidos, que se unem para constituir uma proteína homotetramérica de 56 kDa com uma estrutura secundária de folha ß, que serve como proteína de deslocamento para a tiroxina (T4), e como proteína de ligação ao retinol (vitamina A). O principal local de formação dessa proteína é o fígado, embora uma pequena quantidade seja produzida pelo plexo coroide e pelas células retinianas. O gene codificante da TTR (18q11.2 12) é pequeno (7 kb) e contém quatro éxons. As mutações convertem-se em perda do equilíbrio do tetrâmero proteico. Surgem, então, fibrilas amiloides (FA) em cadeias não ramificadas de 10-12 mm de diâmetro e, em consequência, essas fibrilas indissolúveis se condensam nos tecidos e órgãos. As síndromes clínicas concernentes ao acúmulo da proteína TTR são polineuropatia amiloidótica familiar (PAF-TTR), cardiomiopatias (CMP) e amiloidose sistêmica senil (AAS). Uma estimativa recente da prevalência global relatou a existência de 5.000 a 10.000 casos de PAF-TTR. O presente estudo objetiva elaborar uma plataforma online (plataforma de diagnóstico PAF-TTR) a fim de contribuir para o estudo epidemiológico e facilitar o diagnóstico da doença em nosso país. O projeto baseou-se em pesquisa bibliográfica sistemática com o intuito de estabelecer a fundamentação teórica necessária e, em seguida, utilizou as evidências clínicas e epidemiológicas levantadas na elaboração de uma plataforma que nos auxiliará futuramente como ferramenta facilitadora na investigação da patologia (pesquisa aplicada). O resultado alcançado foi a elaboração desta plataforma, contendo um questionário, que tornará o trabalho dos profissionais mais dinâmico, barato e eficiente, caracterizando melhor a doença em nosso país e promovendo qualidade de vida aos pacientes através do diagnóstico precoce. A plataforma de diagnóstico PAF-TTR poderá se tornar um recurso valioso para a caracterização e o diagnóstico da doença.Amyloidoses are diseases characterized by mutations in the transthyretin coding gene (TTR) located in chromosome 18. The TTR protein, formerly referred to as prealbumin, is composed of a polypeptide chain of 127 amino acid residues that bind to constitute a 56 kDa homotetrameric protein with a secondary β-sheet structure that serves as a transport protein for thyroxine (T4) and retinol binding protein (vitamin A). The main site of synthesis of this protein is the liver, although a small amount is produced by the choroid plexus and retinal cells. The coding gene TTR (18q11.2-12) is small (7 kb) and contains four exons. Mutations result in loss of balance of the protein tetramer. As a result, amyloid fibrils (AF) appear in unbranched chains of 10-12 nm in diameter and consequently these insoluble fibrils condense in tissues and organs. The clinical syndromes concerning the abnormal deposits of the transthyretin protein (TTR) are: familial amyloid polyneuropathies (FAP), cardiomyopathies (CMP), and senile systemic amyloidoses (SSA). OBJECTIVE: This study aims to develop an online platform to facilitate the diagnosis of patients with familial amyloid polyneuropathy (FAP) by mutation of the transthyretin protein (TTR) in the state of Rio de Janeiro. The study was based on bibliographical research in order to obtain the necessary theoretical foundation and in a second moment applied research was used, so that a platform to help as a facilitating tool in the diagnosis of the disease could be created. The use of a questionnaire in the platform is fundamental for a better characterization of the disease. The result achieved was the elaboration of a platform, which will allow the professionals involved a more dynamic, cheaper and more efficient job, therefore bringing a better life opportunity for patients. In this way, the platform can contribute as a facilitating tool for the evolution of an effective method of characterization and diagnosis of this disease57 f

Anti-musk positive myasthenia gravis and three semiological cardinal signs

Myasthenia gravis (MG) is a relatively uncommon disorder with an annual incidence of approximately 7 to 9 new cases per million. The prevalence is about 70 to 165 per million. The prevalence of the disease has been increasing over the past five decades. This is thought to be due to better recognition of the condition, aging of the population, and the longer life span of affected patients. MG causes weakness, predominantly in bulbar, facial, and extra-ocular muscles, often fluctuating over minutes to weeks, in the absence of wasting, sensory loss, or reflex changes. The picture of fluctuating, asymmetric external ophthalmoplegia with ptosis and weak eye closure is virtually diagnostic of myasthenia. We report an atypical MG case with three semiological cardinal signs