Perfil demográfico y clínico-funcional de pacientes con atrofia muscular espinal atendidos en el Instituto Teletón Santiago / Demographic and clinical-functional profile of patients with spinal muscular atrophy attending Instituto Teletón Santiago

Introducción: La atrofia muscular espinal (AME) es una enfermedad neuromuscular (ENM) severa caracterizada por la degeneración de las motoneuronas alfa del asta anterior de la médula espinal, generando una debilidad progresiva de la musculatura proximal. La incidencia mundial se estima en 1/6.000-10.000 nacidos vivos. Contamos con escasos datos de las características de los pacientes con AME en la población chilena. Objetivo: Determinar magnitud, características demográficas y clínico funcionales de los pacientes con AME atendidos en el Instituto Teletón Santiago (ITS). Pacientes y Método: Estudio descriptivo transversal, basado en revisión del sistema informático ITS, fichas clínicas y encuesta telefónica. Resultados: Se identificaron 62 pacientes con AME con controles en ITS, 49 (79%), fueron incluidos. 30,6%, 36,7% y 32,7% corresponden a pacientes con AME 1, 2 y 3 respectivamente. Edad promedio 10,6 ± 6,6 años; pérdida de marcha edad mediana de 6,8 años en pacientes AME 3. 67,3% requieren algún tipo de asistencia ventilatoria, 44,9% presentan trastornos de deglución, 75,5% escoliosis, 49,0% subluxación o luxación de cadera, 79,6% retracciones articulares y 65,3% dolor. En participación, el 83% de las actividades de ocio se realizan dentro del hogar, principalmente de tipo tecnológico; 77,5% realiza salidas sociales. Conclusión: Las características clínico funcionales de los pacientes con AME, evidencian un grupo que presenta un alto nivel de dependencia en todos los tipos de la enfermedad, múltiples comorbilidades y alteraciones músculo-esqueléticas secundarias y por ello requiere de un programa de rehabilitación multidisciplinaria tal como lo describe la literatura internacional.

Introduction: Spinal muscular atrophy (SMA) is a severe neuromuscular disease (NMD) characterized by the loss of alpha motor neurons of the anterior horn of the spinal cord, causing progressive weakness of proximal muscles. Global prevalence is estimated to be 1/6,000-10,000 live births. There is limited data on SMA patients in the Chilean population. Objective: To establish the scale, demographics and functional-clinical characteristics of SMA patients attending Instituto Teletón Santiago (ITS). Patients and Method: Cross-sectional, descriptive study based on the review of ITS's data information system, clinical records and telephone surveys. Results: 62 SMA patients were identified attending regular controls at ITS, 49 (79%) were included in the study. 30.6%, 36.7% and 32.7% correspond to SMA 1, 2 or 3, respectively. Average age 10.6 ± 6.6 years; loss of gait at a median age of 6.8 years in SMA 3 patients. 67.3% require some type of breathing assistance, 44.9% have swallowing problems, 75.5% scoliosis, 49% hip dislocation or subluxation, 79.6% contracture of joints and 65.3% pain. In terms of social participation, 83% of recreational activities are carried out indoors, mainly related to the use of technology; and 77.5% go out to take part in social activities. Conclusion: Functional-clinical characteristics of SMA patients show that there is a group with high levels of dependence in all types of the disease, multiple concurrent disorders and secondary musculoskeletal conditions, and therefore, in the necessity to have a multidisciplinary rehabilitation system, as described in international literature.

Análisis genético molecular en atrofia muscular espinal / Molecular evaluation in infantile spinal muscular atrophy

Introducción: La atrofia muscular espinal de la infancia (AMEi) es una enfermedad neurodegenerativa, causada principalmente por deleciones del gen SMN 1 en su locus 5q11.1-13.3. La severidad va desde el tipo I, que compromete la vida en edades tempranas, hasta el tipo IV. Objetivos: Se describen hallazgos moleculares en pacientes con AME, nacionalmente remitidos al Instituto de Neurología y Neurocirugía así como se reporta la frecuencia por 100.000 habitantes en cada una de las provincias de la isla. Pacientes y Métodos: 105 pacientes fueron estudiados, remitidos entre 1997 y 2011. Para la detección de las deleciones se utilizó la técnica de reacción en cadena de la polimerasa (PCR) con cebadores correspondientes a los exones 7 y 8 del gen SMN 1, y digestión con enzimas DraI y DdeI respectivamente y analizados en gel de agarosa al 2 por ciento. Resultados y Discusión: Se encontró un 59 por ciento diagnosticados como AME I, 28,6 por ciento AME II, 12,4 por ciento AME III. Del total de casos 36,2 por ciento resultaron tener deleción de los exones 7 y 8, 35,2 por ciento deleción del exón 7 solamente y 28,2 por ciento no presentaron deleción de los exones correspondientes. Se discuten dichos resultados de acuerdo a la literatura internacional. Se presentan los resultados de frecuencias por 100.000 habitantes en cada provincia del país y discuten dichas frecuencias de acuerdo a la diversidad ancestral de la población cubana. Se concluye lo novedoso del estudio que constituye el primer reporte en una población caribeña.

Introduction: Infantile Spinal Muscular Atrophy (infantile SMA) is a neurodegenerative disease caused primarily by the deletion of the SMN1 gene at 5q11.1 - 13.3. Its severity ranges from type I, in early childhood, to type IV. Objectives: To describe molecular findings in patients with SMA, who were nationally referred to the Institute of Neurology and Neurosurgery and to describe the frequency per 100,000 people in each province of the island. Patients and Methods: 105 patients, referred between 1997 and 2011, were studied. The polymerase chain reaction (PCR) technique was used to detect the deletions of exons 7 and 8 of the SMN1 gene, and DraI and DdeI enzymes, in 2 percent agarose gel, were used for digestion. Results: 59 percent of the patients were diagnosed with SMA I, 28.6 percent with SMA II and 12.4 percent with SMA III. 36.2 percent of total patients presented deletions of exons 7, 8, 35.2 percent only deletion of exon 7 and 28.2 percentdid not present deletion of exons. Conclusion: These results are discussed according to the international literature. The frequency per 100,000 inhabitants in each province is presented and discussed according to ancestral diversity of the Cuban population. Also, the originality of the study is mentioned as it is the first report of this type in a Caribbean population.

Quantitative Analysis of SMN1 Gene and Estimation of SMN1 Deletion Carrier Frequency in Korean Population based on Real-Time PCR

Spinal muscular atrophy (SMA) is an autosomal recessive disorder, caused by homozygous absence of the survival motor neuron gene (SMN1) in approximately 94% of patients. Since most carriers have only one SMN1 gene copy, several SMN1 quantitative analyses have been used for the SMA carrier detection. We developed a reliable quantitative real-time PCR with SYBR Green I dye and studied 13 patients with SMA and their 24 parents, as well as 326 healthy normal individuals. The copy number of the SMN1 gene was determined by the comparative threshold cycle (Ct) method and albumin was used as a reference gene. The homozygous SMN1 deletion ratio of patients was 0.00 and the hemizygous SMN1 deletion ratio of parents ranged from 0.39 to 0.59. The delta delta Ct ratios of 7 persons among 326 normal individuals were within the carrier range, 0.41-0.57. According to these data, we estimated the carrier and disease prevalence of SMA at 1/47 and 1/8,496 in Korean population, respectively. These data indicated that there would be no much difference in disease prevalence of SMA compared with western countries. Since the prevalence of SMA is higher than other autosomal recessive disorders, the carrier detection method using real-time PCR could be a useful tool for genetic counseling.

Clinical and molecular analysis of spinal muscular atrophy in brazilian patients

As amiotrofias espinhais progressivas (SMAs) constituem as doenças degenerativas de origem genética letais mais comuns do sistema nervoso central e mais freqüentes dentre as doenças autossômicas recessivas após a mucoviscidose. A incidência estimada das SMAs e de aproximadamente 1:10.000 nativivos. Clinicamente, as SMAs säo classificadas em mais grave (doença de Werdnig-Hoffmann, tipo I), intermediária (tipo II) e tardia e benigna (doença de Kugelberg-Welander, tipo III). O gene para os três tipos de SMAs foi mapeado no cromossomo 5q11.2-13.3. Foram identificados dois genes candidatos na mesma regiäo: SMN (sobrevida do neurônio motor) e NAIP (proteína inibidora de apoptose neuronal). Estudamos ambos genes em 87 pacientes brasileiros (20 tipo I, 14 tipo II e 53 tipo III) pertencentes a 74 famílias, utilizando as técnicas de PCR e SSCP. Foi encontrada deleçäo nos exons 7 e/ou 8 do gene SMN em 69 por cento das famílias: 16/20 na tipo I, 9/12 na tipo II e 26/42 na tipo III. Dentre as 51 famílias com deleçäo, 44 tiveram deleçäo no exon 5 do gene NAIP foi encontrada em 7/20 na tipo I, 2/12 na tipo II e 1/42 na tipo III. Näo foi encontrada deleçäo nos genes SMN e NAIP nos 112 progenitores, 26 irmandades assintomáticas e 104 controles normais. Näo houve correlaçäo entre deleçäo de um ou ambos genes com a gravidade do quadro clínico.