ABSTRACT
BACKGROUND: Adult-onset spinal muscular atrophy (SMA) represents an expanding group of inherited neurodegenerative disorders in clinical practice. OBJECTIVE: This review aims to synthesize the main clinical, genetic, radiological, biochemical, and neurophysiological aspects related to the classical and recently described forms of proximal SMA. METHODS: The authors performed a non-systematic critical review summarizing adult-onset proximal SMA presentations. RESULTS: Previously limited to cases of SMN1-related SMA type 4 (adult form), this group has now more than 15 different clinical conditions that have in common the symmetrical and progressive compromise of lower motor neurons starting in adulthood or elderly stage. New clinical and genetic subtypes of adult-onset proximal SMA have been recognized and are currently target of wide neuroradiological, pathological, and genetic studies. CONCLUSIONS: This new complex group of rare disorders typically present with lower motor neuron disease in association with other neurological or systemic signs of impairment, which are relatively specific and typical for each genetic subtype.
Subject(s)
Motor Neuron Disease , Muscular Atrophy, Spinal , Radiology , Adult , Humans , Muscular Atrophy, Spinal/genetics , Neurophysiology , Rare DiseasesABSTRACT
Abstract Background: Adult-onset spinal muscular atrophy (SMA) represents an expanding group of inherited neurodegenerative disorders in clinical practice. Objective: This review aims to synthesize the main clinical, genetic, radiological, biochemical, and neurophysiological aspects related to the classical and recently described forms of proximal SMA. Methods: The authors performed a non-systematic critical review summarizing adult-onset proximal SMA presentations. Results: Previously limited to cases of SMN1-related SMA type 4 (adult form), this group has now more than 15 different clinical conditions that have in common the symmetrical and progressive compromise of lower motor neurons starting in adulthood or elderly stage. New clinical and genetic subtypes of adult-onset proximal SMA have been recognized and are currently target of wide neuroradiological, pathological, and genetic studies. Conclusions: This new complex group of rare disorders typically present with lower motor neuron disease in association with other neurological or systemic signs of impairment, which are relatively specific and typical for each genetic subtype.
RESUMO Antecedentes: Atrofia muscular espinhal (AME) de início no adulto representa um grupo de doenças neurodegenerativas hereditárias em expansão na prática clínica. Objetivo: Este artigo de revisão sintetiza os principais aspectos clínicos, genéticos, radiológicos, bioquímicos e neurofisiológicos relacionados às formas clássicas e recentemente descritas de AME proximal do adulto. Métodos: Os autores realizaram uma revisão crítica não sistemática descrevendo as principais apresentações de AME proximal de início no adulto. Resultados: Previamente restrito às apresentações de AME tipo 4 associada ao gene SMN1, este grupo atualmente envolve mais de 15 diferentes condições clínicas que compartilham entre si a presença de comprometimento progressivo e simétrico do neurônio motor inferior se iniciando no adulto ou no idoso. Novos subtipos clínicos e genéticos de AME proximal de início no adulto foram reconhecidas e são alvos atuais de estudos direcionados a aspectos neurorradiológicos, patológicos e genéticos. Conclusões: Este novo grupo complexo de doenças raras tipicamente se apresenta com doença do neurônio motor inferior em associação com outros sinais de comprometimento neurológico ou sistêmico, os quais apresentam padrões relativamente específicos para cada subtipo genético.
Subject(s)
Humans , Radiology , Muscular Atrophy, Spinal/genetics , Motor Neuron Disease , Rare Diseases , NeurophysiologyABSTRACT
BACKGROUND: Acute hepatic porphyrias represent an expanding group of complex inherited metabolic disorders due to inborn errors of metabolism involving heme biosynthesis. OBJECTIVE: We aimed to review the main clinical and therapeutic aspects associated with acute hepatic porphyrias. METHODS: The authors provided a wide non-systematic review of current concepts and recently acquired knowledge about acute hepatic porphyrias. RESULTS: Acute neurovisceral attacks are the most common and life-threatening presentation of this group and are often considered the main clinical manifestation by clinicians during differential diagnosis and the start of proper diagnostic work-up for acute porphyrias. However, atypical presentations with central nervous system involvement, neuropsychiatric disturbances, and some subtypes with photosensitivity usually make the definite diagnosis difficult and late. Early therapeutic interventions are essential during emergency treatment and intercritical periods to avoid recurrent severe presentations. The availability of new disease-modifying therapeutic proposals based on small interfering RNA (siRNA)-based therapies, complementary to the classic intravenous glucose infusion and hemin-based treatments, emphasizes the importance of early diagnosis and genetic counseling of patients. CONCLUSIONS: This review article highlights the main biochemical, pathophysiological, clinical, and therapeutic aspects of acute hepatic porphyrias in clinical practice.
Subject(s)
Porphyria, Acute Intermittent , Porphyrias, Hepatic , Humans , Neurologists , Porphobilinogen Synthase , Porphyria, Acute Intermittent/diagnosis , Porphyria, Acute Intermittent/therapy , RNA, Small InterferingABSTRACT
OBJECTIVE: The aim of the study was to report the proportion of homozygous and compound heterozygous variants in the survival motor neuron 1 (SMN1) gene in a large population of patients with spinal muscular atrophy (SMA) and to correlate the severity of the disease with the presence of specific intragenic variants in SMN1 and with the SMN2 copy number. METHODS: Four hundred fifty Brazilian patients with SMA were included in a retrospective study, and clinical data were analyzed compared with genetic data; the SMN2 copy number was obtained by multiplex ligation-dependent probe amplification and pathogenic variants in SMN1 by next-generation sequencing. RESULTS: Four hundred two patients (89.3%) presented homozygous exon 7-SMN1 deletion, and 48 (10.7%) were compound heterozygous for the common deletion in one allele and a point mutation in the other allele. Recurrent variants in exons 3 and 6 (c.460C>T, c.770_780dup and c.734_735insC) accounted for almost 80% of compound heterozygous patients. Another recurrent pathogenic variant was c.5C>G at exon 1. Patients with c.770_780dup and c.734_735insC had a clinical phenotype correlated with SMN2 copy number, whereas the variants c.460C>T and c.5C>G determined a milder phenotype independently of the SMN2 copies. CONCLUSIONS: Patients with specific pathogenic variants (c.460C>T and c.5C>G) presented a milder phenotype, and the SMN2 copy number did not correlate with disease severity in this group.
Subject(s)
Spinal Muscular Atrophies of Childhood/diagnosis , Child , Diagnosis, Differential , Humans , MaleABSTRACT
PURPOSE: To critically analyze the inclusion of individuals with special needs in regular education in Brazil, considering social and legal aspects, through literature review. RESEARCH STRATEGY: The literature search was conducted in open access databases: LILACS, SciELO, Portal Cochrane and IUSDATA, the latter belonging to the Library of the Law School of the University of São Paulo, considering all articles published until December 2010. The search strategy used the following keywords: inclusive education; special education; inclusive proposal; individuals with special needs. SELECTION CRITERIA: In the search, only studies in which the summary or the body of the article were related to the purpose of the study were evaluated and selected. DATA ANALYSIS: The potentially relevant articles for review were presented in a protocol form containing the eligibility criteria of the study, methods used, characteristics of the analyzed group or manuscripts, type of intervention used in the study, and results obtained. Articles classified as expert opinions, despite their low level of scientific evidence, were considered in this work, since they are often found in the literature on the issue. RESULTS: A total of 1,399 articles was found and 120 potentially relevant articles were selected after reading their abstracts. From these, 67 articles were cited in more than one database, which resulted in 53 articles to be fully read. Fifteen of these articles were excluded after reading because they did not meet the inclusion criteria. Thus, 38 studies were included and analyzed. CONCLUSION: Following a critical analysis of the literature in the field, it was concluded that, so far, in general, the school receives individuals with special needs; however, there is a long way to go to actually include these individuals, although Brazil has the scope of inclusion. Therefore, it is necessary to establish public policies and guidelines aimed at effective inclusion.
Subject(s)
Disabled Persons/education , Mainstreaming, Education/legislation & jurisprudence , Social Adjustment , Brazil , Humans , StudentsABSTRACT
OBJETIVOS: Analisar criticamente a inclusão do portador de necessidades especiais no ensino regular brasileiro, considerando aspectos sociais e jurídicos, por meio de revisão de literatura. ESTRATÉGIA DE PESQUISA: A pesquisa bibliográfica foi conduzida em bases de dados de acesso público: LILACS, SciELO, Portal Cochrane e IUSDATA, sendo esta última da Biblioteca da Faculdade de Direito da Universidade de São Paulo, considerando todos os artigos publicados até o mês de dezembro de 2010. Como estratégia de busca foram utilizados os seguintes termos livres: educação inclusiva, educação especial, proposta inclusiva e portador de necessidades especiais. CRITÉRIOS DE SELEÇÃO: Durante a busca, foram avaliados e selecionados apenas os estudos cujo resumo ou corpo do artigo tivesse relação com o objetivo proposto. ANÁLISE DE DADOS : Os artigos potencialmente relevantes para a revisão foram apresentados em uma ficha protocolar contendo critérios de elegibilidade do estudo, métodos utilizados, características do grupo de artigos analisado, tipo de intervenção realizada e resultados obtidos no estudo. Os artigos classificados como opinião de especialistas, apesar de apresentarem baixo nível de evidência científica, foram incluídos no trabalho, pois são frequentemente encontrados na literatura sobre o assunto. RESULTADOS: Foram encontrados 1.399 artigos, e após leitura dos resumos foram selecionados 120 artigos potencialmente relevantes considerando-se o objetivo da pesquisa. Destes, 67 artigos foram citados em mais de uma base de dados, o que resultou em 53 artigos para serem lidos na íntegra. Após a leitura dos 53 artigos, foram excluídos 15 que não se enquadravam nos critérios de inclusão. Desta forma, 38 estudos foram incluídos e analisados. CONCLUSÃO: Após a análise crítica da literatura da área conclui-se que, até o momento, de maneira geral, a escola recebe, mas há muito a percorrer para incluir os alunos portadores de necessidades especiais, embora o país possua o escopo da inclusão. Assim, faz-se necessário o estabelecimento de diretrizes e ações políticas visando uma inclusão efetiva.
PURPOSE: To critically analyze the inclusion of individuals with special needs in regular education in Brazil, considering social and legal aspects, through literature review. RESEARCH STRATEGY: The literature search was conducted in open access databases: LILACS, SciELO, Portal Cochrane and IUSDATA, the latter belonging to the Library of the Law School of the University of São Paulo, considering all articles published until December 2010. The search strategy used the following keywords: inclusive education; special education; inclusive proposal; individuals with special needs. SELECTION CRITERIA: In the search, only studies in which the summary or the body of the article were related to the purpose of the study were evaluated and selected. DATA ANALYSIS: The potentially relevant articles for review were presented in a protocol form containing the eligibility criteria of the study, methods used, characteristics of the analyzed group or manuscripts, type of intervention used in the study, and results obtained. Articles classified as expert opinions, despite their low level of scientific evidence, were considered in this work, since they are often found in the literature on the issue. RESULTS: A total of 1,399 articles was found and 120 potentially relevant articles were selected after reading their abstracts. From these, 67 articles were cited in more than one database, which resulted in 53 articles to be fully read. Fifteen of these articles were excluded after reading because they did not meet the inclusion criteria. Thus, 38 studies were included and analyzed. CONCLUSION: Following a critical analysis of the literature in the field, it was concluded that, so far, in general, the school receives individuals with special needs; however, there is a long way to go to actually include these individuals, although Brazil has the scope of inclusion. Therefore, it is necessary to establish public policies and guidelines aimed at effective inclusion.