Distrofia muscular de Duchenne: imunoexpressão da alfa-distroglucana na musculatura esquelética e associação com performance cognitiva.
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Data
2004
Tipo
Dissertação de mestrado
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Título de Volume
Resumo
A distrofia muscular de Duchenne (DMD) é uma distrofia muscular que se expressa com déficit cognitivo em 20-30% dos casos. Apesar do cérebro destas crianças parecer normal, já foram encontradas alterações diversas, não explicando, porém o acometimento cognitivo. O gene da distrofina é muito grande e codifica a distrofina em várias isoformas. Deleções e duplicações em locais de ligação às isoformas distais como a Dp140, Dp71 favorecem a incidência de retardo mental. A distrofina se liga a um complexo de proteínas (CPAD), entre
elas, as distroglicanas. Dentro do complexo das distroglicanas, a α-distroglicana tem sido demonstrada como importante no mecanismo, não só de estabilização da musculatura esquelética à contração e relaxamento musculares, mas também na sinaptogênese, migração neuronal e plasticidade neuronal. Seus diferentes
papéis, na musculatura esquelética e no sistema nervoso central (SNC), nos levam a pensar sobre os mecanismos envolvidos em sua deficiência, bem como da distrofina, na fisiopatologia do déficit cognitivo dos pacientes com DMD. Foram
avaliados 19 pacientes com DMD, sendo encontrada uma alta proporção (42,1%)
com quociente de inteligência (QI) abaixo da média. Os pacientes apresentavam
na época da biopsia muscular, entre 4 anos e 2 meses e 10 anos e 5 meses; e,
na época das avaliações, entre 6 e 12 anos de idade. Dos 19 pacientes, 2 foram
avaliados pelo Stanford-Binet. Dos 17 pacientes avaliados pelo WISC-III, 52,9%
apresentaram um QI verbal menor do que a faixa média de inteligência, sendo
que destes 29,4% um QI abaixo de 70. A proporção de pacientes com QI verbal
dentro da faixa média de inteligência, isto é, entre a média inferior e a média
superior, foi de 47%. Em nossa amostra de musculatura esquelética de biopsias
de pacientes com DMD, obteve-se que, 89,5% dos pacientes apresentaram a
imunoexpressão da α-distroglicana entre 0 e 25% do total das fibras musculares.
Porém, um indivíduo apresentou uma imunoexpressão de 70,4%, e outro de
43,2%, ambos com performance cognitiva dentro da faixa média de inteligência,
achado este não mencionado em literatura. Não houve uma relação
estatisticamente significante entre os valores de QI total, verbal e de execução
com a imunoexpressão da α-distroglicana em fragmentos musculares destes
pacientes. A presença da α-distroglicana no cérebro, bem como da distrofina,
sugere o seu papel na fisiopatologia do déficit cognitivo das crianças com DMD.
Os mecanismos que envolvem a inteligência são complexos. Podemos atribuir
fatores genéticos, estruturais, mas também devemos considerar os fatores
ambientais e psicossociais, no caso de nossos pacientes, de grande valia no que
se refere à carência de estímulos e oportunidades de aprendizado.
The Duchenne muscular Dystrophy (DMD) is a muscular dystrophy with cognitive impairment present in 20-30% of the cases. Despite of the fact that theses children’s brain looks like normal, it has already been bound a great variety of abnormalities, however not explaining the cognitive impairment. The dystrophin gene is very large and encodes several dystrophin isoforms. Deletions and duplications in linking sites to distal isoforms like Dp140, Dp71 favor mental retardation incidence. The dystrophin connects to a proteic complex (CDG), among these proteins, the dystroglicans. Within the dystroglycan complex, the α-dystroglycan, have been known as important in several mechanisms, not only at skeletal muscle stabilization at muscular contraction, but also at synaptogenesis, neuronal migration, neuronal plasticity. Its different roles, at skeletal muscle and Central Nervous System (CNS), bring us to think about the mechanisms involved when it is deficient, as well, as the dystrophin, at cognitive impairment physiopathology in DMD patients. Nineteen DMD patients were assessed, and a high proportion (42%) performed the intelligence quotient (IQ) below the average. The patients aged at the time of the muscle biopsy, between 4 and ten years, and, at the assessment time, between 6 and 12 years old. Among the 19 patients, 2 were assessed by the Stanford-Binet. Among the 17 assessed by WISC-III, 52.9% performed a verbal IQ below the average, and 29.4% below 70. The proportion of patients who performed an average verbal IQ, was 47%. In our muscle biopsies samples of DMD patients, 89.5% presented α-dystroglycan immunostaining between 0 and 25%. However, one patient presented a α-dystroglycan immunostaining of 70.4%, and the other 43.2% and who performed an average IQ, finding not mentioned in literature. There was no significant statistic relationship among total IQ, verbal IQ and execution IQ and α-dystroglycan immunostaining at these patients muscle samples. The presence of α-dystroglycan in the brain, as well as, the dystrophin, suggest their role on the pathophysiology of cognitive impairment in DMD children. The mechanisms involved in intelligence are complex. We can atribute genetic factor, structural ones, but also consider the environment and psychosocials ones, in the case of our patients, worthy if we consider the lack of stimulus and learning opportunities.
The Duchenne muscular Dystrophy (DMD) is a muscular dystrophy with cognitive impairment present in 20-30% of the cases. Despite of the fact that theses children’s brain looks like normal, it has already been bound a great variety of abnormalities, however not explaining the cognitive impairment. The dystrophin gene is very large and encodes several dystrophin isoforms. Deletions and duplications in linking sites to distal isoforms like Dp140, Dp71 favor mental retardation incidence. The dystrophin connects to a proteic complex (CDG), among these proteins, the dystroglicans. Within the dystroglycan complex, the α-dystroglycan, have been known as important in several mechanisms, not only at skeletal muscle stabilization at muscular contraction, but also at synaptogenesis, neuronal migration, neuronal plasticity. Its different roles, at skeletal muscle and Central Nervous System (CNS), bring us to think about the mechanisms involved when it is deficient, as well, as the dystrophin, at cognitive impairment physiopathology in DMD patients. Nineteen DMD patients were assessed, and a high proportion (42%) performed the intelligence quotient (IQ) below the average. The patients aged at the time of the muscle biopsy, between 4 and ten years, and, at the assessment time, between 6 and 12 years old. Among the 19 patients, 2 were assessed by the Stanford-Binet. Among the 17 assessed by WISC-III, 52.9% performed a verbal IQ below the average, and 29.4% below 70. The proportion of patients who performed an average verbal IQ, was 47%. In our muscle biopsies samples of DMD patients, 89.5% presented α-dystroglycan immunostaining between 0 and 25%. However, one patient presented a α-dystroglycan immunostaining of 70.4%, and the other 43.2% and who performed an average IQ, finding not mentioned in literature. There was no significant statistic relationship among total IQ, verbal IQ and execution IQ and α-dystroglycan immunostaining at these patients muscle samples. The presence of α-dystroglycan in the brain, as well as, the dystrophin, suggest their role on the pathophysiology of cognitive impairment in DMD children. The mechanisms involved in intelligence are complex. We can atribute genetic factor, structural ones, but also consider the environment and psychosocials ones, in the case of our patients, worthy if we consider the lack of stimulus and learning opportunities.
Descrição
Citação
PEREIRA, Conceição Campanario da Silva. Distrofia muscular de Duchenne: imunoexpressão da alfa-distroglucana na musculatura esquelética e associação com performance cognitiva. 2004. 92 f. Dissertação (Mestrado em Ciências) - Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, 2004.