Atrofia muscular espinhal: diagnóstico, tratamento e perspectivas futuras / Spinal muscular atrophy: diagnosis, treatment and future prospects

OBJETIVO: Relatar as recentes descobertas genéticas e moleculares, juntamente com as perspectivas futuras, para o tratamento da atrofia muscular espinhal, auxiliando, dessa forma, os profissionais da área da saúde a fazerem um rápido diagnóstico e proporcionarem um suporte terapêutico correto e precoce. FONTES DOS DADOS: As informações foram coletadas a partir de artigos científicos publicados nas duas últimas décadas, pesquisados nas bases de dados SciELO, PubMed e MEDLINE. SÍNTESE DOS DADOS: A atrofia muscular espinhal é uma doença neurodegenerativa com herança genética autossômica recessiva. É causada por uma deleção homozigótica do gene de sobrevivência do motoneurônio. Essa alteração genética resulta na redução dos níveis da proteína de sobrevivência do motoneurônio, levando à degeneração de motoneurônios alfa da medula espinhal, o que resulta em fraqueza e paralisia muscular proximal progressiva simétrica. Sabe-se que alguns cuidados básicos referentes à nutrição, respiração e fisioterapia podem ser importantes para retardar o progresso da doença e prolongar a vida dos pacientes. Vários medicamentos estão sendo testados, alguns novos, outros já conhecidos, como o ácido valproico, sendo que a paralisia pode ser estacionada, mas não revertida. CONCLUSÕES: A atrofia muscular espinhal é uma desordem de difícil diagnóstico, por ser pouco conhecida, e de tratamento ainda incerto. Os tratamentos farmacológicos e as terapias de suporte existentes ainda não são capazes de recuperar os motoneurônios ou as células musculares que já foram perdidos, mas têm o objetivo de retardar o progresso da doença e melhorar a função muscular residual dos pacientes, bem como oferecer uma melhor qualidade e expectativa de vida.

OBJECTIVE: To report on recent genetic and molecular discoveries and on future prospects for the treatment of spinal muscular atrophy (SMA), thereby helping healthcare professionals to make a quick diagnosis and provide appropriate and timely therapeutic support. SOURCES: Information was collected from scientific articles published in the last 2 decades, retrieved from the databases SciELO, PubMed, and MEDLINE. SUMMARY OF THE FINDINGS: SMA is a neurodegenerative disorder with autosomal recessive genetic heredity. It is caused by a homozygous deletion of the survival motor neuron (SMN1) gene. This genetic alteration results in reduced levels of the SMN protein, leading to degeneration of alpha motor neurons of the spinal cord and resulting in muscle weakness and progressive symmetrical proximal paralysis. It is known that basic nutritional and respiratory care and physiotherapy can be important to delaying disease progression and prolonging patients' lives. Several drugs are being tested, some new, others, such as valproic acid, already known; paralysis can be halted, but not reversed. CONCLUSIONS: SMA is a difficult to diagnose disorder, because it is little known, and treatment is uncertain. Pharmacological treatments and supportive therapies are not yet able to recover motor neurons or muscle cells that have already been lost, but are aimed at delaying disease progression and improving patients' residual muscle function, as well as offering better quality of life and life expectancy.

Detection of homozygous and heterozygous SMN deletions of spinal muscular atrophy in a single assay with multiplex ligation-dependent probe amplification / 北京大学学报(医学版)

Objective: Spinal muscular atrophy(SMA), an autosomal recessive neuromuscular degeneration of the anterior horn cells of the spinal cord and brain stem, results in one of the most common diseases with muscle fatigue and atrophy. Most SMA cases including all the types are due to the homozygous deletion of at least exon 7 within the survival motor neuron 1 (SMN-1) gene. Although a "golden standard" assay (PCR with mismatch primer followed by enzyme digestion) is very reliable for the identification of homozygous SMN-1 deletion, the carrier detection of heterozygous SMN-1 deletion remains a challenge. Methods: Some PCR-based gene dosage assays or multiplex PCR allow for the determination of the copy number of SMN-1 gene to identify heterozygous deletion, but these procedures are often time consuming and available on a limited clinical basis. Recently developed MLPA (multiplex ligation-dependent probe amplification) is an efficient procedure that can accurately analyze relative quantification to establish the copy number of the SMN gene. We performed a validation for simultaneous detection of homozygous SMN-1 deletions of SMA patients and heterozygous SMN-1 deletions of SMA carriers in a simple assay using a MLPA-SMA assay specific reagent. Results: Six out of 20 patients with SMA were found to have homozygous SMN-1 deletion, confirmed by the PCR/digestion assay. All 4 parents of the children with SMA had heterozygous SMN-1 deletion, confirmed by an independent relative quantitative analysis. Conclusion: MLPA provides a simple, rapid and accurate method of simultaneously detecting homozygous deletions and heterozygous deletions in a single assay for both SMN-1 and SMN-2 genes.