Patient perspective: my rare disease journey.

My underlying diagnosis since birth was congenital muscular dystrophy not otherwise specified Being born in 1970 meant that there were no genetic testing, no standards of care, and no true understanding of the pathology that separates one congenital-onset neuromuscular disorder from the next. Two muscle biopsies described histological abnormalities of small type 1 fibers and were among the first of M.H. Brooke's cases described as congenital fiber-type disproportion (Brooke, Experta Medica 295: 147 [1973]).

International retrospective natural history study of LMNA-related congenital muscular dystrophy.

Muscular dystrophies due to heterozygous pathogenic variants in LMNA gene cover a broad spectrum of clinical presentations and severity with an age of onset ranging from the neonatal period to adulthood. The natural history of these conditions is not well defined, particularly in patients with congenital or early onset who arguably present with the highest disease burden. Thus the definition of natural history endpoints along with clinically revelant outcome measures is essential to establishing both clinical care planning and clinical trial readiness for this patient group. We designed a large international cross-sectional retrospective natural history study of patients with genetically proven muscle laminopathy who presented with symptoms before two years of age intending to identify and characterize an optimal clinical trial cohort with pertinent motor, cardiac and respiratory endpoints. Quantitative statistics were used to evaluate associations between LMNA variants and distinct clinical events. The study included 151 patients (median age at symptom onset 0.9 years, range: 0.0-2.0). Age of onset and age of death were significantly lower in patients who never acquired independent ambulation compared to patients who achieved independent ambulation. Most of the patients acquired independent ambulation (n = 101, 66.9%), and subsequently lost this ability (n = 86; 85%). The age of ambulation acquisition (median: 1.2 years, range: 0.8-4.0) and age of ambulation loss (median: 7 years, range: 1.2-38.0) were significantly associated with the age of the first respiratory interventions and the first cardiac symptoms. Respiratory and gastrointestinal interventions occurred during first decade while cardiac interventions occurred later. Genotype-phenotype analysis showed that the most common mutation, p.Arg249Trp (20%), was significantly associated with a more severe disease course. This retrospective natural history study of early onset LMNA-related muscular dystrophy confirms the progressive nature of the disorder, initially involving motor symptoms prior to onset of other symptoms (respiratory, orthopaedic, cardiac and gastrointestinal). The study also identifies subgroups of patients with a range of long-term outcomes. Ambulatory status was an important mean of stratification along with the presence or absence of the p.Arg249Trp mutation. These categorizations will be important for future clinical trial cohorts. Finally, this study furthers our understanding of the progression of early onset LMNA-related muscular dystrophy and provides important insights into the anticipatory care needs of LMNA-related respiratory and cardiac manifestations.

Hypoglycemia in patients with congenital muscle disease.

BACKGROUND: Only a few small studies have previously reported episodes of hypoglycemia in children with neuromuscular diseases; however, there has been no broader investigation into the occurrence of hypoglycemia in children with congenital muscle disease (CMD). METHODS: Pediatric patients enrolled in the CMD International Registry (CMDIR) with a history of hypoglycemia were included in this retrospective review. Hypoglycemic episodes and associated clinical and biochemical characteristics were characterized. RESULTS: Ten patients with CMD (5 with LAMA2-related muscular dystrophy) reported at least one episode of hypoglycemia beginning at an average age of 3.5 years. Predominant symptoms included altered mental status and nausea/vomiting, and laboratory studies demonstrated metabolic acidosis and ketonuria, consistent with ketotic hypoglycemia. CONCLUSION: Patients with CMD may have an increased risk of hypoglycemia during fasting, illness, or stress due to their relatively low muscle mass and hence, paucity of gluconeogenic substrate. Clinicians should therefore maintain a high index of suspicion for hypoglycemia in this high-risk patient population and caregivers should routinely be trained to recognize and treat hypoglycemia.

Mortality and respiratory support in X-linked myotubular myopathy: a RECENSUS retrospective analysis.

PURPOSE: Individuals with X-linked myotubular myopathy (XLMTM) who survive infancy require extensive supportive care, including ventilator assistance, wheelchairs and feeding tubes. Half die before 18 months of age. We explored respiratory support and associated mortality risk in RECENSUS, particularly among patients ≤5 years old who received respiratory support at birth; this subgroup closely matches patients in the ASPIRO trial of gene therapy for XLMTM. DESIGN: RECENSUS is an international, retrospective study of patients with XLMTM. Descriptive and time-to-event analyses examined survival on the basis of age, respiratory support, tracheostomy use, predicted mutational effects and life-sustaining care. RESULTS: Outcomes for 145 patients were evaluated. Among 126 patients with respiratory support at birth, mortality was 47% overall and 59% among those ≤5 years old. Median survival time was shorter for patients ≤5 years old than for those >5 years old (2.2 years (IQR 0.7-5.6) vs 30.2 years (IQR 19.4-30.2)). The most common cause of death was respiratory failure (66.7%). Median survival time was longer for patients with a tracheostomy than for those without (22.8 years (IQR 8.7-30.2) vs 1.8 years (IQR 0.2-not estimable)). The proportion of patients living without a tracheostomy was 50% at age 6 months and 28% at age 2 years. Median survival time was longer with provision of life-sustaining care than without (19.4 years (IQR 3.1-not estimable) vs 0.2 years (IQR 0.1-2.1)). CONCLUSIONS: High mortality, principally due to respiratory failure, among patients with XLMTM ≤5 years old despite respiratory support underscores the need for early diagnosis, informed decision-making and disease-modifying therapies. TRIAL REGISTRATION NUMBER: NCT02231697.

Common Data Elements for Muscle Biopsy Reporting.

CONTEXT: There is no current standard among myopathologists for reporting muscle biopsy findings. The National Institute of Neurological Disorders and Stroke has recently launched a common data element (CDE) project to standardize neuromuscular data collected in clinical reports and to facilitate their use in research. OBJECTIVE: To develop a more-uniform, prospective reporting tool for muscle biopsies, incorporating the elements identified by the CDE project, in an effort to improve reporting and educational resources. DESIGN: The variation in current biopsy reporting practice was evaluated through a study of 51 muscle biopsy reports from self-reported diagnoses of genetically confirmed or undiagnosed muscle disease from the Congenital Muscle Disease International Registry. Two reviewers independently extracted data from deidentified reports and entered them into the revised CDE format to identify what was missing and whether or not information provided on the revised CDE report (complete/incomplete) could be successfully interpreted by a neuropathologist. RESULTS: Analysis of the data highlighted showed (1) inconsistent reporting of key clinical features from referring physicians, and (2) considerable variability in the reporting of pertinent positive and negative histologic findings by pathologists. CONCLUSIONS: We propose a format for muscle-biopsy reporting that includes the elements in the CDE checklist and a brief narrative comment that interprets the data in support of a final interpretation. Such a format standardizes cataloging of pathologic findings across the spectrum of muscle diseases and serves emerging clinical care and research needs with the expansion of genetic-testing therapeutic trials.

Respuesta emocional de los pobladores afectados por los huracanes / Emotional response in people affected by hurricanes

Desde un enfoque psicológico podemos definir un desastre como un hecho inesperado y de por sí catastrófico .Los individuos y las comunidades, en mayor o menor medida, lo perciben como un evento vital estresante. Se realizó un estudio descriptivo retrospectivo con el objetivo de evaluar la respuesta de los pobladores de la circunscripción 48 del Municipio San Luis, Pinar del Río, afectados por los huracanes Isidore y Lily que causaron grandes daños en esta zona. El universo estuvo constituido por 52 adultos que se corresponde con la muestra, a los cuales se les aplicó una encuesta que recoge dentro de sus principales aspectos: síntomas ante la inminencia y después de ocurrido el evento .Se obtuvo como principales resultados que los síntomas antes del fenómeno atmosférico fueron: preocupación y miedo. 20 días después predominó la tristeza, trastornos del sueño, dificultades con hábitos alimentarios e higiénicos, inseguridad, uso excesivo de alcohol (en algunos hombres),nerviosismo, angustia, desolación, asociado a los daños ocurridos en los hogares y las casas de tabaco. La enfermera y el médico de familia, unidos a los medios de información y las organizaciones políticas y de masas, jugaron un papel fundamental antes y después del evento, llegando a la conclusión de que con la prevención oportuna sobre los factores estresantes se reduce la aparición de síntomas graves o tardíos en la esfera psíquica, siendo fundamental una actuación multidisciplinaria con base comunitaria(AU)

Starting from a psychological approach, a disaster can be defined as an unexpected event and catastrophic in its nature. To a large or lesser extent, individuals and communities perceived natural disasters as events which cause stress. A descriptive and retrospective study was conducted with the purpose of assessing peoples response during natural events at No- 48 district in San Luis municipality, Pinar del Rio, mainly those affected by Isidore and Lily hurricanes which provoked severe damages in this territory. The target group was comprised of 52 adults in correspondence with the sample. A survey was applied considering the following aspects: previous and subsequent symptoms to the hurricane occurrence. The main symptoms before hurricane were: concern and fear. 20 days after: sadness, sleep disorders, difficulties with food and hygiene habits, insecurity, and disproportionate alcohol intake (in a number of men), feelings of nervousness, anxiety, and distress as well, associated with damages in homes and tobacco houses. Family nurse and doctor, together with mass media, political and peoples organizations play a very important role before and after the event. Opportune prevention, concerning stressful factors, reduces the onset of severe or late symptoms in psychical sphere, and a multidisciplinary performance having a community support is essential(AU)