Nutritional Issues among Children with Duchenne Muscular Dystrophy-Incidence of Deficiency and Excess Body Mass.

The progression of Duchenne muscular dystrophy (DMD)requires the assessment of nutritional disturbances at each stage of the disease. The purpose of this study was to assess the nutritional status in various ages of boys with DMD using screening and in-depth evaluation methods. Body composition by Dual X-ray Absorptiometry (DXA), basal metabolic rate (BMR) by indirect calorimetry, a questionnaire of nutritional status-Pediatric Nutrition Screening Tool (PNST)-and laboratory parameters were performed. In the cohort of 93 boys aged 8.54 (5.9-12.6 years), inappropriate nutritional status occurred in 41.8% of boys (underweight 11.8%, overweight 16.0%, and obesity 14.0%). In the 10-13 age group, the occurrence of overweight and underweight was the highest. Based on PNST, 15.1% of patients were at nutritional risk (≥2 points)-the most in the 14-17 age group (29%). A negative correlation was identified between PNST and z-scores of body weight, BMI, and FFMI (r Spearman = -0.49, -0.46, and -0.48, respectively; p < 0.05). There were no differences between BMR results from indirect calorimetry and calculations from the Schofield formula for any age group. In obese boys, the caloric requirement in indirect calorimetry was significantly lower than that indicated by the calculations according to the Schofield formula (p < 0.028). Inappropriate nutritional status occurred in almost half of the children with DMD. The age group in which nutritional disorders were most frequently identified was 10-13 years old. PNST could be considered a tool for screening malnutrition after testing a larger group of DMD patients.

Disease-associated comorbidities, medication records and anthropometric measures in adults with Duchenne muscular dystrophy.

We investigated the comorbidities, associated factors, and the relationship between anthropometric measures and respiratory function and functional abilities in adults with Duchenne muscular dystrophy (DMD). This was a single-centre cross-sectional study in genetically diagnosed adults with DMD (>16 years old). Univariate and multivariate analyses identified factors associated with dysphagia, constipation, Body Mass Index (BMI), and weight. Regression analysis explored associations between BMI, weight, and respiratory/motor abilities. We included 112 individuals (23.4 ± 5.2 years old), glucocorticoid-treated 66.1 %. The comorbidities frequency was 61.6 % scoliosis (61.0 % of them had spinal surgery), 36.6 % dysphagia, 36.6 % constipation, and 27.8 % urinary conditions. The use of glucocorticoids delayed the time to spinal surgery. The univariate analysis revealed associations between dysphagia and constipation with age, lack of glucocorticoid treatment, and lower respiratory and motor function. In the multivariate analysis, impaired cough ability remained as the factor consistently linked to both conditions. Constipation associated with lower BMI and weight. BMI and weight positively correlated with respiratory parameters, but they did not associate with functional abilities. Glucocorticoids reduce the frequency of comorbidities in adults with DMD. The ability to cough can help identifying dysphagia and constipation. Lower BMI and weight in individuals with DMD with compromised respiratory function may suggest a higher calories requirement.

Patient- and caregiver-reported impact of symptoms in Duchenne muscular dystrophy.

INTRODUCTION/AIMS: To better understand the disease burden faced by individuals with Duchenne muscular dystrophy (DMD) of all ages and elucidate potential targets for therapeutics, this study determined the prevalence and relative importance of symptoms experienced by individuals with DMD and identified factors associated with a higher disease burden. METHODS: We conducted qualitative interviews with individuals with DMD and caregivers of individuals with DMD to identify potential symptoms of importance to those living with DMD. We subsequently performed a cross-sectional study to assess which symptoms have the highest prevalence and importance in DMD and to determine which factors are associated with a higher disease burden. RESULTS: Thirty-nine individuals, aged 11 years and above, provided 3262 quotes regarding the symptomatic burden of DMD. Two hundred participants (87 individuals with DMD and 113 caregivers) participated in a subsequent cross-sectional study. Individuals with DMD identified limitations with mobility or walking (100%), inability to do activities (98.9%), trouble getting around (97.6%), and leg weakness (97.6%) as the most prevalent and life altering symptomatic themes in DMD. The symptomatic themes with the highest prevalence, as reported by caregivers on behalf of those with DMD for whom they care, were limitations with mobility or walking (90.3%), leg weakness (89.2%), and emotional issues (79.6%). Steroid/glucocorticoid use (e.g., prednisone or deflazacort) was associated with a lower level of disease burden in DMD. DISCUSSION: There are many symptomatic themes that contribute to disease burden in individuals with DMD. These symptoms are identified by both individuals with DMD and their caregivers and have a variable level of importance and prevalence in the DMD population.

Observing the Clinical Course of Duchenne Muscular Dystrophy in Medicaid Real-World Healthcare Data.

INTRODUCTION: Duchenne muscular dystrophy (DMD) is a rare, severe progressive neuromuscular disease. Health insurance claims allow characterization of population-level real-world outcomes, based on observed healthcare resource use. An analysis of data specific to those with Medicaid insurance is presently unavailable. The objective was to describe the real-world clinical course of DMD based on claims data from Medicaid-insured individuals in the USA. METHODS: Individuals with DMD were identified from the MarketScan Multi-State Medicaid datasets (2013-2018). Diagnosis and procedure codes from healthcare claims were used to characterize the occurrence of DMD-relevant clinical observations; categories were scoliosis, cardiovascular-related, respiratory and severe respiratory-related, and neurologic/neuropsychiatric. Age-restricted analyses were conducted to focus on the ages at which DMD-relevant clinical observations were more likely to be captured, and to better understand the impact of both age and follow-up time. RESULTS: Of 2007 patients with DMD identified, median (interquartile range) age at index was 14 (9-20) years, and median follow-up was 3.1 (1.6-4.7) years. Neurologic and neuropsychiatric observations were most frequently identified, among 49.3% of the cohort; followed by cardiovascular (48.5%), respiratory (38.1%), scoliosis (36.3%), and severe respiratory (25.0%). Prevalence estimates for each category were higher when analyzed within age-restricted subgroups; and increased as follow-up time increased. CONCLUSIONS: This study is the first to use diagnosis and procedure codes from real-world Medicaid claims to document the clinical course in DMD. Findings were consistent with previously published estimates from commercially insured populations and clinical registries; and contribute to the expanding body of real-world evidence around clinical progression of patients with DMD.

Epilepsy in Duchenne and Becker muscular dystrophies.

OBJECTIVE: Duchenne and Becker muscular dystrophies (DMD and BMD) are dystrophinopathies caused by variants in DMD gene, resulting in reduced or absent dystrophin. These conditions, characterized by muscle weakness, also manifest central nervous system (CNS) comorbidities due to dystrophin expression in the CNS. Prior studies have indicated a higher prevalence of epilepsy in individuals with dystrophinopathy compared to the general population. Our research aimed to investigate epilepsy prevalence in dystrophinopathies and characterize associated electroencephalograms (EEGs) and seizures. METHODS: We reviewed 416 individuals with dystrophinopathy, followed up at three centers between 2010 and 2023, to investigate the lifetime epilepsy prevalence and characterize EEGs and seizures in those individuals diagnosed with epilepsy. Associations between epilepsy and type of dystrophinopathy, genotype, and cognitive involvement were studied. RESULTS: Our study revealed a higher epilepsy prevalence than the general population (1.4%; 95% confidence interval: 0.7-3.2%), but notably lower than previously reported in smaller dystrophinopathy cohorts. No significant differences were found in epilepsy prevalence between DMD and BMD or based on underlying genotypes. Cognitive impairment was not found to be linked to higher epilepsy rates. The most prevalent epilepsy types in dystrophinopathies resembled those observed in the broader pediatric population, with most individuals effectively controlled through monotherapy. INTERPRETATION: The actual epilepsy prevalence in dystrophinopathies may be markedly lower than previously estimated, possibly half or even less. Our study provides valuable insights into the epilepsy landscape in individuals with dystrophinopathy, impacting medical care, especially for those with concurrent epilepsy.

Respiratory comorbidities and treatments in Duchenne muscular dystrophy: impact on life expectancy and causes of death.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a neuromuscular disorder with progressive decline of pulmonary function increasing the risk of early mortality. The aim of this study was to explore the respiratory-related comorbidities, and the effect of these comorbidities and treatments on life expectancy and causes of death. METHODS: All male patients living in Sweden with DMD, born and deceased 1970-2019, were included. Data regarding causes of death were collected from the Cause of Death Registry and cross-checked with the medical records along with diagnostics and relevant clinical features. RESULTS: Hundred and twenty nine patients were included with a median lifespan of 24.3 years. Acute respiratory failure accounted for 63.3% of respiratory-related causes of death. 70.1% suffered at least one pneumonia, with first episode at a median age of 17.8 years. Hypoventilation was found in 73.0% with onset at 18.1 years. 60.5% had their first pneumonia before established hypoventilation. Age at onset of hypoventilation showed a strong correlation with age at first pneumonia. First pneumonia and scoliosis non-treated with scoliosis surgery increased the risk of dying of respiratory-related causes. In 10% of the patients, first pneumonia resulted in acute tracheostomy or early death. Patients treated with assisted ventilation had higher life expectancy compared to untreated patients. CONCLUSIONS: Our results highlight the importance of identifying subclinical hypoventilation in a timely manner and the importance of an active treatment regime upon clinical signs of pneumonia.

Patient's perspective about research landscape for rare diseases in India.

I am writing this piece as the parent of a son diagnosed with Duchenne muscular dystrophy, a severely debilitating disease that not only impairs skeletal muscles of the limbs but is also life-threatening due to progressive weakening of the cardiac and diaphragm muscles. I have traversed the harrowing diagnostic, treatment, and management odyssey of a typical rare disease (RD) patient in India.

Burden of Disease of Duchenne Muscular Dystrophy in Denmark - A National Register-Based Study of Individuals with Duchenne Muscular Dystrophy and their Closest Relatives.

Background: Duchenne Muscular Dystrophy (DMD) is a progressive genetic disease with a prevalence of 1 per 3,600-6,000 male births. Individuals with DMD are typically diagnosed at age 4-7 years; median survival is 30 years. They require multidisciplinary care, personal assistance, and often special education. Objective: The aim was to assess the burden of disease in DMD in Denmark. This includes incidence, prevalence, use of healthcare services, labour market participation, educational outcomes, and overall attributable costs due to DMD. Impact on the closest relatives (siblings and parents) was also investigated. Methods: The comprehensive Danish national health and administrative registers were used to assess the burden of disease following individuals with DMD and closest relatives from five years before, and up to 20 years after DMD diagnosis. Individuals with DMD (and relatives) from 1994-2021 were included. All outcomes were compared to matched control groups without the disease drawn from the Danish population. Results: 213 unique individuals with DMD were identified. They had lower grades in school, required more special education and more healthcare and home care compared to their control group. The extra costs of special education summed to EUR 180,900 over the course of 11 years elementary school. They had an annual average productivity loss of EUR 20,200 between the age of 18 to 30. The extra healthcare costs of DMD in the 20 years after diagnosis were estimated to EUR 1,524,000. If an individual with DMD lives to be 30, total extra costs sum to EUR 2,365,800. Conclusions: Using national register data this study presented detailed results on the burden of disease of DMD, including impact on closest relatives. With 60 additional hospital admissions and 200 extra outpatient contacts in 20 years healthcare costs, but also costs of home care and special education, increases as disease progresses.

[Subjective oral health, malocclusions and oral health related quality of life in patients with Duchenne muscular dystrophy]. / De subjectieve mondgezondheid, malocclusies en orale kwaliteit van leven van patiënten met Duchenne-spierdystrofie.

Duchenne muscular dystrophy is a hereditary progressive neuromuscular disorder. Deterioration and weakening of the muscles is also present in orofacial muscles. Both weakness of the muscles and the fact that patients become more dependent of care, can make oral care more difficult. At this moment, it is unknown how patients with Duchenne muscular dystrophy experience their oral health and which problems regarding oral health and oral care may impact their oral health related quality of life. In this cross-sectional study, we found that, despite a high percentage of gingivitis, a high percentage of patients who experience halitosis and a high percentage of malocclusions, patients score their oral health related quality of life as good.

Self- and Caregiver-Reported Participation, Quality of Life, and Related Mood and Behavior Challenges in People Living With Dystrophinopathies.

BACKGROUND: Previous studies of quality of life (QOL), mood, and behavior in muscular dystrophy focus on caregiver perceptions. This cross-sectional study aims to determine the prevalence of clinically significant mood and behavior problems by both patient and caregiver report and assess relationship between mood/behavior and QOL. METHODS: Forty-one patients with dystrophinopathies (Duchenne muscular dystrophy [DMD] and Becker muscular dystrophy [BMD]) were recruited through the University of Virginia Neuromuscular Clinic. Each patient and caregiver dyad completed questionnaires, including the Behavior Assessment System for Children, 2nd Edition (BASC-2); the Pediatric Quality of Life Inventory for DMD (PedsQL-DMD); Children's Depression Inventory, 2nd Edition; and Screen for Child Anxiety Related Disorders. RESULTS: Persons with dystrophinopathies rated most of their behavior and adaptive skills similarly to the general population. Sixty-four percent of parent assessments rated clinically significant problems on the BASC-2. Worse BASC-2 scores for self- and parent assessments correlated with lower (worse) scores in the Worry and Communication PedsQL domains. Patient-reported QOL scores were higher than parent-reported scores in each domain except Worry. CONCLUSIONS: Individuals with DMD/BMD rate their adaptive skills, behavioral symptoms, externalizing and internalizing problems, and school problems more positively than parents/caregivers. Obtaining self-report data is a worthwhile endeavor that can add value to intervention planning, with the ultimate goal of optimizing QOL.

Responsiveness of upper limb scales and trunk control for the evolution of patients with duchenne muscular dystrophy / Responsividade de escalas de membro superior e controle de tronco na evolução de pacientes com distrofia muscular de duchenne

ABSTRACT Objective: To verify the interval of responsiveness to the scales Segmental Assessment of Trunk Control (SATCo-BR), Performance of Upper Limbs (PUL), and Jebsen Taylor Test (JTT) in patients with Duchenne Muscular Dystrophy (DMD). Methods: We assessed patients with DMD aged 6 to 19 years old and with mini-mental (MMSE) score above 10 points. The assessments were performed individually, in a single session. The upper limb function was performed by PUL and JTT, and trunk control by SATCo-BR. Assessments were repeated six and 12 months after the initial assessment. The repeated-measures analysis of variance model and Bonferroni's multiple comparison method were employed as post hoc analysis; when the ANOVA assumptions were not met, the Friedman test was applied. Results: The sample consisted of 28 patients evaluated in three moments (initial, and six and 12 months after the beginning). There was a time effect for the Upper Limb function performance in the total JTT, and for the subtests, except for subtests 1 and 6, which did not show a difference between the different moments. There was also a time effect for the score of total PUL, proximal PUL, intermediate PUL, and distal PUL. In the SATCo-BR, this effect was observed between the initial and 6 months, and between the initial and 12 months. Conclusions: The JTT, PUL, and SATCo-BR scales can detect changes over time, and they showed responsiveness to detect the evolution of the disease in the 6-month interval.

RESUMO Objetivo: Verificar o intervalo de tempo para a responsividade das escalas Segmental Assessment of Trunk Control (SATCo-BR), Performance of Upper Limb (PUL) e o Teste de Função Manual de Jebsen Taylor (TJT) em pacientes com distrofia muscular de Duchenne (DMD). Métodos: Foram avaliados pacientes com DMD nas idades entre 6 e 19 anos, e com escore do Mini Exame do Estado Mental (MEEM) a partir de 10 pontos. As avaliações foram realizadas individualmente, em uma única sessão: a função de membro superior (MS) ocorreu pela PUL e TJT; e da do controle de tronco, pela SATCo-BR. As avaliações foram repetidas após seis e 12 meses da avaliação inicial. Foi empregado o modelo de análise de variância com medidas repetidas e o método de comparações múltiplas de Bonferroni, como análise post hoc; quando os pressupostos da ANOVA não foram atendidos, foi aplicado o teste de Friedman. Resultados: A amostra foi composta por 28 pacientes avaliados em três momentos (inicial, após seis meses e após 12 meses). Houve efeito do tempo no desempenho da função Membro Superior no TJT total e nos subtestes, exceto nos subtestes 1 e 6, que não apresentaram diferença nas avaliações entre os diferentes momentos. Houve efeito do tempo para o escore da PUL total, PUL proximal, PUL intermediário e PUL distal. No SATCo-BR, esse efeito foi entre o inicial e após seis meses, e entre o inicial e após 12 meses. Conclusões: As escalas TJT, PUL e SATCo-BR são capazes de detectar alterações ao longo do tempo, e apresentam responsividade para detectar a evolução da doença em intervalo de 6 meses.

Functional performance and muscular strength in symptomatic female carriers of Duchenne muscular dystrophy / Desempenho funcional e força muscular em portadoras sintomáticas de distrofia muscular de Duchenne

Abstract Duchenne muscular dystrophy (DMD) usually affects men. However, women are also affected in rare instances. Approximately 8% of female DMD carriers have muscle weakness and cardiomyopathy. The early identification of functional and motor impairments can support clinical decision making. Objective: To investigate the motor and functional impairments of 10 female patients with dystrophinopathy diagnosed with clinical, pathological, genetic and immunohistochemical studies. Methods: A descriptive study of a sample of symptomatic female carriers of DMD mutations. The studied variables were muscular strength and functional performance. Results: The prevalence was 10/118 (8.4%) symptomatic female carriers. Deletions were found in seven patients. The age of onset of symptoms in female carriers of DMD was quite variable. Pseudohypertrophy of calf muscles, muscular weakness, compensatory movements and longer timed performance on functional tasks were observed in most of the cases. Differently from males with DMD, seven female patients showed asymmetrical muscular weakness. The asymmetric presentation of muscle weakness was frequent and affected posture and functionality in some cases. The functional performance presents greater number of compensatory movements. Time of execution of activities was not a good biomarker of functionality for this population, because it does not change in the same proportion as the number of movement compensations. Conclusion: Clinical manifestation of asymmetrical muscle weakness and compensatory movements, or both can be found in female carriers of DMD mutations, which can adversely affect posture and functional performance of these patients.

Resumo A distrofia muscular de Duchenne (DMD) geralmente afeta indivíduos do sexo masculino. No entanto, mulheres também são acometidas em casos raros. Aproximadamente 8% das portadoras de DMD têm fraqueza muscular ou cardiomiopatia. A identificação precoce das alterações funcionais e motoras pode alterar a tomada de decisão clínica. Objetivo: Investigar as deficiências motoras e funcionais de 10 pacientes do sexo feminino com distrofinopatia diagnosticada por estudos clínicos, patológicos, genéticos e imuno-histoquímicos. Método: Estudo descritivo de uma amostra de portadoras sintomáticas de mutações DMD. As variáveis estudadas foram força muscular e desempenho funcional. Resultados: A prevalência foi de 10/118 (8,4%) de portadoras sintomáticas de DMD. Foram encontradas deleções em sete pacientes. A idade de início dos sintomas em portadoras de DMD foi variável. Pseudo-hipertrofia de panturrilhas, movimentos compensatórios, fraqueza muscular e aumento no tempo de execução de tarefas funcionais foram observados na maioria dos casos. Diferentemente dos homens com DMD, sete pacientes apresentaram fraqueza muscular assimétrica. A apresentação assimétrica da fraqueza muscular foi frequente, podendo afetar a postura e a funcionalidade. O desempenho funcional geralmente apresenta aumento no número de movimentos compensatórios. Não podemos sempre considerar o tempo como um bom marcador de funcionalidade para essa população, uma vez que não muda na mesma proporção que o número de compensações em todas essas pacientes. Conclusão: Fraqueza muscular assimétrica e movimentos compensatórios, ou ambos, podem ser encontrados em portadoras sintomáticas de DMD, o que pode afetar a postura e a funcionalidade dessas pacientes.

Prevalencia de dolor crónico en pacientes con distrofia muscular de Duchenne en etapas no ambulantes / Prevalence of chronic pain in Duchenne muscular dystrophy patients in non-ambulatory stage

INTRODUCTION: Chronic pain is a frequent symptom in patients with Duchenne muscular dystrophy (DMD) as reported, in up to 73%, affecting their normal activities, participation and quality of life; however it is an underdiagnosed symptom, and therefore, undertreated. OBJECTIVE: to establish the prevalence of chronic pain in a population with non-ambulatory DMD attending Instituto Teletón Santiago (ITS). MATERIALS AND METHODS: Descriptive, cross-sectional study in DMD patients of Instituto Teletón Santiago, of 12 years old and older, who were in an early or late non-ambulatory stage. By means of a questionnaire designed by the authors, adapted from 'Brief Pain Inventory' and 'ID-Pain', and administered via telephone, it was possible to obtain data on the presence of acute, chronic pain and its intensity, frequency, location, clinical characteristics and interference with daily life activities and the use of analgesic drugs. Data collected helped to do an estimation of the prevalence of pain in the last week, chronic pain as well as summary measures for location, intensity and clinical characteristics. RESULTS: of 74 active patients with DMD and in compliance with the inclusion criteria, 23 subjects responded the questionnaire (31% response rate); average age was 18.3 years, and 9 months since loss of walking ability; prevalence of acute pain was 13% and 13% for chronic pain; most common localization was in the hips, followed by neck, spine and lower limbs; duration and frequency were variable and of moderate intensity. CONCLUSION: Pain has a lower prevalence in the studied population compared to the literature, however, it affects multiple locations and has an impact on their daily activities, and therefore it is important to record the presence of chronic pain in clinical practice. It is necessary to get a higher response rate in future studies and quantify pain with an instrument developed especially for this population.

INTRODUCCIÓN: El dolor crónico es un síntoma frecuente en pacientes con distrofia muscular de Duchenne (DMD) reportado en hasta un 73%, afectando las actividades, participación y calidad de vida; sin embargo, es un síntoma subdiagnosticado y por ende subtratado. OBJETIVO GENERAL: Determinar prevalencia de dolor crónico en población con DMD en etapa no ambulante que se atiende en Instituto Teletón Santiago (ITS). MATERIALES Y MÉTODOS: Estudio descriptivo, transversal en pacientes con DMD, activos en Instituto Teletón Santiago, de 12 años y más de edad, que se encontraban en etapa no ambulante temprano o tardío. Mediante la aplicación de un cuestionario diseñado por los autores adaptando Brief Pain Inventory e ID-Pain, aplicado vía telefónica, se obtuvo datos sobre la presencia de dolor agudo, crónico, intensidad, frecuencia, localización, tiempo de duración, características clínicas del dolor, interferencia en actividades de vida diaria y uso de fármacos analgésicos. Con los datos recolectados se estimó la prevalencia de dolor crónico, de la última semana y medidas de resumen para localización, intensidad y características clínicas. RESULTADOS: De 74 pacientes activos con diagnóstico de DMD que cumplían criterios de inclusión, se encuestaron 23 sujetos (porcentaje de respuesta de 31%); edad promedio de 18,3 años y 9 años desde pérdida de la marcha; la prevalencia de dolor agudo fue de 13% y de dolor crónico 13%; la localización más frecuente fue en las caderas, seguido por cuello y columna y extremidades inferiores, de duración y frecuencia variable e intensidad moderada. CONCLUSIÓN: El dolor tiene menor prevalencia en la población estudiada en relación con la literatura, sin embargo, afecta múltiples localizaciones e impacta en sus actividades de la vida diaria, por lo que es importante consignar la presencia de dolor crónico en la práctica clínica. Se hace necesario obtener un mayor porcentaje de respuesta en futuros estudios y cuantificar el dolor con un instrumento confeccionado especialmente para esta población.

Las distrofias musculares en la literatura, el cine y la televisión / Muscular dystrophies in literature, cinema and television

Introducción. Las distrofias musculares son enfermedades hereditarias, producidas por una mutación genética, lentas o rápidamente progresivas, que afectan fundamentalmente a la musculatura estriada. Existen diversas formas clínicas, y las más frecuentes son la distrofia muscular de Duchenne y la distrofia muscular de Becker. Objetivo. Analizar cómo se han representado las distrofias musculares en la literatura, el cine y la televisión. Desarrollo. La distrofia muscular ha sido reflejada en la literatura, el cine y la televisión. En algunos casos sólo se menciona, en otros tiene un papel secundario en la trama y en otros es un personaje principal el que sufre la enfermedad. Generalmente se hace referencia a la enfermedad de Duchenne, y con menos frecuencia a la de Becker, aunque en algunos casos sólo se menciona que el paciente presenta distrofia muscular, sin especificar a qué variedad clínica pertenece. Podemos encontrar obras de testimonio, novelas, cómics, largometrajes de ficción, documentales, cortos y programas televisivos que pretenden dar a conocer la enfermedad y sus implicaciones, y concienciar a la población sobre la necesidad de invertir recursos en la investigación. Conclusiones. La distrofia muscular ha sido representada con realismo en la literatura, el cine y la televisión, y la distrofia muscular de Duchenne es la variedad clínica que se ha mostrado más habitualmente. Se han reflejado los síntomas, la evolución, el pronóstico, el papel de la familia y los cuidadores, la sexualidad, los tratamientos paliativos, el espíritu de superación, y la necesidad de concienciar a la sociedad y de invertir más recursos en investigación

Introduction. Muscular dystrophies are inherited disorders, produced by a genetic mutation, with a slow or rapid progression, that basically affect striated muscle tissue. There are several clinical forms, the most frequent being Duchenne's muscular dystrophy and Becker muscular dystrophy. Aim. To analyse how muscular dystrophies have been portrayed in literature, cinema and television. Development. Muscular dystrophy is a disorder that has been reflected in literature, cinema and television. In some cases it is only mentioned, sometimes it plays a secondary role in the plot, and in others it is the lead character who suffers from the disease. In general, reference is made to Duchenne's disease and, albeit less frequently, to Becker muscular dystrophy, although in some cases the patient is just said to be suffering from muscular dystrophy, without specifying what clinical variety it belongs to. Testimonials, novels, comics, fiction films, documentaries, short films and television programmes have all been produced with the aim of making the disease and its implications more widely known, as well as making the public aware of the need to invest resources in research. Conclusions. Muscular dystrophy has been portrayed quite realistically in literature, cinema and television, and Duchenne's muscular dystrophy is the clinical variety that has been shown most often. Aspects that have been reflected include its symptoms, progression, prognosis, the role of the family and caregivers, sexuality, palliative care, patients' will to overcome difficulties and the need to raise society's awareness of the condition and to invest more resources in research

Asociaciones de pacientes y autorización de nuevos fármacos en Estados Unidos. El caso del eteplirseno para la distrofia muscular de Duchenne / Patients organizations and new drug approval in the US. Eteplirsen and Duchenne muscular dystrophy case

Introducción. En 2016, la Agencia de Medicamentos y Alimentos (FDA) estadounidense autorizó la comercialización del eteplirseno para el tratamiento de la distrofia muscular de Duchenne. Este hecho ha sido muy controvertido, por cuanto la autorización se produjo tras una evaluación negativa por parte del comité asesor de la FDA y de sus propios técnicos. Fue la directora del Centro de Investigación y Evaluación de Fármacos quien autorizó el medicamento, decisión que no revocó el director de la FDA. Objetivo. Informar sobre los acontecimientos más relevantes que han conducido a la autorización del eteplirseno por la FDA. Desarrollo. En el artículo se exponen pormenorizadamente los hechos relevantes que acontecieron durante el desarrollo clínico y la evaluación reguladora del eteplirseno siguiendo la vía de la ‘autorización acelerada’. Se comentan las razones por las que los técnicos de la FDA entienden que este medicamento no ha mostrado producir beneficio clínico, la actitud de las asociaciones de pacientes y las exigencias postautorización que la FDA ha impuesto a la compañía propietaria del medicamento. Por último, se reflexiona sobre la situación en que quedan los pacientes españoles una vez que el eteplirseno está comercializado en Estados Unidos. Conclusiones. Este caso, único en la historia de autorización de medicamentos en el mundo occidental, pone de manifiesto las dificultades que las regulaciones actuales de autorización acelerada de nuevos medicamentos pueden tener en la interpretación de datos del desarrollo clínico, cuando éstos son escasos y de poca calidad, y cuando se trata de enfermedades raras sin terapias disponibles (AU)

Introduction. In 2016 the US Food and Drug Administration (FDA) granted the marketing authorization for eteplirsen for Duchenne muscular dystrophy. This has been a very controversial decision since it happened after a negative assessment from both the Advisory Committee and the technical FDA evaluation team. The FDA’s Center for Drug Evaluation and Research (CDER) director was who ultimately approved the product, while the FDA Commissioner did not overrule that decision. Aim. To report about the most relevant events regarding the approval of eteplirsen by the US FDA. Development. All relevant facts that occurred during the clinical development and evaluation phase following "accelerated approval" procedure of eteplirsen are discussed in detail. The technical FDA evaluation team reasons supporting that the drug has not proven clinical benefit, the attitude of patient advocacy groups and the post-approval FDA requirements to the marketing authorization holder are discussed. Finally, we reflect on what is the situation Spanish patients face once eteplirsen is on the US market. Conclusions. This is a unique case in the history of drug authorizations in western countries, that shows the difficulties thatcurrent regulations on accelerated approval of new medicines could have when interpreting scarce and low quality clinical development data, when dealing with rare diseases with no available therapies (AU)

Traducción y validación de la escala Individualized Neuromuscular quality of life para la población española: evaluación de la calidad de vida para personas afectas de enfermedades neuromusculares / Translation and validation of the Individualised Neuromuscular Quality of Life scale for the Spanish population: quality of life assessment for persons with neuromuscular diseases

Introducción. La escala Individualized Neuromuscular Quality of Life (INQoL) es un cuestionario que valora la calidad de vida relacionada con la salud de personas adultas con enfermedades neuromusculares. Objetivo. Validar y analizar la fiabilidad de la versión española de la INQoL, como instrumento de medición de la calidad de vida relacionada con la salud en individuos con enfermedades neuromusculares. Pacientes y métodos. Se realiza una traducción-retrotraducción de la INQoL en la población española y, posteriormente, para el análisis de fiabilidad se llevan a cabo dos mediciones, test-retest, a 50 pacientes de 19 a 67 años. De este modo se evalúa la concordancia intraobservador y se evalúa la consistencia interna de la escala. Resultados. El estudio de la fiabilidad del índice de concordancia intraobservador tiene un valor de excelente en siete de las diez subdimensiones y en la puntuación total de la calidad de vida; de buena, en dos; y de moderada, en una. El análisis del alfa de Cronbach para las subdimensiones de la INQoL tiene un valor de excelente (> 0,818) en siete de ellas, así como en la puntuación total de la calidad de vida relacionada con la salud (0,928), un valor de buena consistencia interna en tres de las subdimensiones y de moderada en una. Conclusiones. La versión española de la INQoL es un instrumento válido y fiable como herramienta de medición de la calidad de vida en individuos adultos con enfermedades neuromusculares (AU)

Introduction. The Individualized Neuromuscular Quality of Life (INQoL) is a questionnaire that evaluates the quality of life related to the health of adults with neuromuscular diseases. Aim. To validate and analyze the reliability of the Spanish version of the INQoL scale as an instrument for measuring quality of life related to health in individuals with neuromuscular diseases. Patients and methods. A translation-back translation of the INQoL in the Spanish population is performed and, subsequently, for the analysis of reliability, two measurements are carried out; test retest, with 50 patients aged between 19 and 67 years. In this way we assess the intraobserver concordance and assess the internal consistency of the scale. Results. The study of the reliability of the intraobserver concordance index has a value of excellent in seven of the ten subdimensions as well as in the total score of the quality of life. It has a value of good in two and of moderate in one subdimension. The analysis of Cronbach’s alpha for the subdimensions of the INQoL has a value of excellent (> 0.818) in seven of them, as well as in the total score of the quality of life related to health (0.928), a value of good internal consistency in three of the subdimensions, and of moderate in one. Conclusions. The Spanish version of the INQoL is a valid and reliable instrument as a tool for measuring quality of life in adult patients with neuromuscular diseases (AU)

Distrofia muscular de Duchenne: incidencia, prevalencia, características sociodemográficas y clínicas de pacientes ingresados a Teletón Chile desde 1993 a 2013 / Duchenne muscular dystrophy: incidence, prevalence, sociodemographic and clinical characteristics of patients admitted to Teletón Chile from 1993 to 2013

Duchenne muscular dystrophy (DMD) in their natural evolution leads to loss of ambulation between 7 and 13 years of age and death in adolescence close to 20 years. The estimated global incidence is of 1/3,500 male births; data in Chile is unknown. Objective: To estimate the incidence, prevalence of DMD and to describe clinical and sociodemographic characteristics of patients admitted to Teletón-Chile between 1993 and 2013. Patients and Method: A descriptive, retrospective, longitudinal study with review of medical records and database at Teletón. 462 DMD patients were admitted during the study period. Results: The incidence and prevalence in Teletón was of 1/6,558 male live births and the prevalence of 11.51 [CI 10.46 to 12.56] 105 men < 30 years. The average age of first consultation was 6.7 +/- 3.4 years, with mild or moderate functional level (65.6 percent). At the end of the study 67 percent were wheelchair users, with medical prescription at 10.8 +/- 3.3 years. 52.2 percent of patients were classified as extreme poverty, attended at Teletón centers of the central region (55.2 percent), and current average age of 14.7 +/- 5.7 years. 35.9 percent of DMD patients were dead at an average age of 18.1 +/- 3.5 years. Conclusion: The incidence and prevalence rates of DMD live births for males < 30 years admitted to Teletón, have declined between 1993-2011; as well as the average age of first consultation. The loss of ambulation and the average age of death are comparable with the current literature...

La distrofia muscular de Duchenne (DMD) en su evolución natural, produce pérdida de deambulación entre los 7 y 13 años de edad y la muerte en la adolescencia cercana a los 20 años. La incidencia mundial se estima de 1/3.500 nacimientos masculinos; en Chile se desconoce su magnitud. Objetivo: Estimar tasas de incidencia, prevalencia de DMD y describir características clínicas y sociodemográficas de pacientes ingresados a Institutos Teletón-Chile (IT) entre 1993 y 2013. Pacientes y Método: Estudio descriptivo, retrospectivo, longitudinal, con revisión de fichas clínicas y base de datos de IT. Se identificaron 462 pacientes con DMD, ingresados en el período estudiado. Resultados: La tasa de incidencia en IT fue de 1/6.558 nacidos vivos masculinos y prevalencia de 11,51 [IC: 10,46-12,56] por 105 varones < 30 años. Edad media de primera consulta: 6,7 +/- 3,4 años, con compromiso funcional leve o moderado (65,6 por ciento); al término del estudio el 67 por ciento eran usuarios de silla de ruedas, con prescripción médica a los 10,8 +/- 3,3 años. 52,2 por ciento de los pacientes de extrema pobreza, atendidos en IT zona central del país (55,2 por ciento), edad promedio actual de 14,7 +/- 5,7 años. El 35,9 por ciento estaban fallecidos, a la edad promedio de 18,1 +/- 3,5 años. Conclusión: Las tasas de incidencia y prevalencia de DMD para los nacidos vivos varones < 30 años ingresados a los IT, han disminuido entre 1993-2011; también la edad promedio de primera consulta. La pérdida de la marcha y la edad media de la defunción, son comparables con la literatura...

Identificación de deleciones en el gen de la distrofina y detección de portadoras en familias con distrofia muscular de Duchenne/Becker / Identifying deletions in the dystrophin gene and detecting carriers in families with duchenne's/becker's muscular dystrophy

Introducción. Del 60 al 65% de las mutaciones que causan distrofia muscular de Duchenne/Becker (DMD/DMB)corresponden a deleciones en el gen de la distrofina. La identificación de deleciones confirma el diagnóstico y permite la detección precisa de portadoras, que es el recurso principal de prevención. En el sudeste de México se desconoce la frecuencia y distribución de las deleciones del gen DMD. Objetivos. Identificar deleciones del gen DMD y detectar portadoras en familiascon DMD/DMB del sudeste de México. Pacientes y métodos. Se incluyeron 26 familias cuyo propósito mostró signos clínicos de DMD/DMB. Las deleciones se determinaron en el ADN de 40 varones mediante reacción en cadena de la polimerasa (PCR) múltiple de 22 segmentos del gen. La detección de portadoras se aplicó a 33 familiares femeninos con PCR mediante polimorfismo de longitud de fragmentos de restricción de los marcadores Pert 87.8/Taq 1, pERT 87.15/Bam H1, y PCR simplepara el VNTR MPIP mediante análisis de ligamiento. Resultados. Las deleciones se identificaron en el 67,5% de pacientes con DMD y se localizaron en el extremo 5’ y en la región central, exones 44 al 52, del gen. En la detección de portadoras, el 73,33% de las familias resultó informativo. Los marcadores 87.8/Taq I y MPIP arrojaron el mayor poder de información, con el 26,67 y el 33,33%, respectivamente. De 33 mujeres, 21 (63,64%) resultaron portadoras, una (3,03%) no portadora y 11 (33.33%) no fueron informativas. Conclusión. La frecuencia de deleciones fue del 67,5%. Se determinó el estado de portador en el 66,67% de las mujeres analizadas. Los marcadores pERT 87.8/Taq 1 y MPIP arrojaron el mayor poder de información

Introduction. Between 60 and 65% of the mutations that cause Duchenne’s/Becker’s muscular dystrophy (DMD/BMD)are deletions in the dystrophin gene. Identifying deletions confirms the diagnosis and allows carriers to be detected with precision, which is the main preventive resource. The frequency and distribution of deletions in the DMD gene is unknown in south-east Mexico. Aims. To identify deletions in the DMD gene and to detect carriers in families with DMD/BMD in south-eastMexico. Patients and methods. The study involved 26 families that showed clinical signs of DMD/BMD. Deletions were determined in the DNA of 40 males by means of the multiple polymerase chain reaction (PCR) in 22 segments of the gene. Detection of carriers was applied to 33 female relatives using PCR-restriction fragment length polymorphism of the polymorphicmarkers Pert 87.8/Taq 1, pERT 87.15/Bam H1, and single PCR for VNTR MP1P by linkage analysis. Results. Deletionswere identified in 67.5% of patients with DMD and they were located in the 5’ end and in the central region, exons 44 to 52, of the gene. In the detection of carriers, 73.33% of the families were informative. The markers 87.8/Taq 1 and MPIP yielded thegreatest information power, with 26.67 and 33.33%, respectively. Of a total of 33 females, 21 (63.64%) were carriers, one (3.03%) was a non-carrier and 11 (33.33%) were not informative. Conclusions. The frequency of deletions was 67.5%. Carrier status was determined in 66.67% of the females who were analysed. The markers pERT 87.8/Taq 1 and MP1P yielded the greatest information power

Distrofia muscular de Duchenne, presentación clínica / Duchenne muscular dystrophy clinical presentation

Background: Duchenne Muscular Dystrophy is an X-link recessive disorder that affects 1 per 3.500 males. Becker Muscular Dystrophy is less common, affecting approximately 1 per 30 000 males. Both diseases are the result of a mutation in the Xp21 gene that encodes for dystrophin. Objective: Describe the clinical manifestations of Duchenne Muscular Dystrophy in patients at our institution. Method: Observational and descriptive study, in which clinical records of 8 patients with Duchenne Muscular Dystrophy were reviewed, with description of their clinical aspects. Results: The mean age at diagnosis was 5 years-old. 6 boys presented developmental delay and 7 deambulation difficulties, being the main reason for medical attendance. 3 patients died during the study period. Conclusions: A multidisciplinary management is required to delay the disease evolution, while it does not have a curative treatment. It is necessary to know the clinical aspects representative of this disease, in order to perform an early diagnosis.

Introducción: La distrofia muscular de Duchenne es una alteración ligada al X recesiva que afecta 1 en 3 500 varones. La distrofia muscular de Becker es menos común, afectando aproximadamente 1 en 30 000 varones. Ambas resultan de la mutación de un gen localizado en Xp21, el cual codifica a la distrofina. Objetivos: Describir el comportamiento clínico de la distrofia muscular de Duchenne en pacientes evaluados en nuestra institución. Pacientes y Métodos: Se realizó un estudio de tipo observacional y descriptivo, donde se revisaron las historias clínicas de ocho pacientes con el diagnóstico de distrofia muscular de Duchenne, donde se describieron los aspectos clínicos y paraclínicos de la entidad. Resultados: El promedio de la edad para el momento del diagnóstico fue de cinco años. Seis presentaron retardo del desarrollo psicomotor y la marcha se encontró alterada en siete pacientes siendo este el principal motivo de consulta junto a caídas frecuentes. Tres pacientes habían fallecido al final del período en estudio. Conclusiones: Se requiere de un tratamiento multidisciplinario para retrasar la evolución de la enfermedad, mientras no se disponga de un tratamiento curativo. Es necesario conocer los aspectos representativos de esta enfermedad para realizar su diagnóstico precoz.

Normalización transitoria de CK en un paciente con distrofia de Becker y tumor germinal testicular; ¿un efecto de la quimioterapia? / Transient normalisation of CK in a patient with Becker muscular dystrophy and testicular germ cell tumor: an effect of chemotherapy?

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