RESUMEN
BACKGROUND: Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetically determined muscle disorders. TRAPPC11-related LGMD is an autosomal-recessive condition characterised by muscle weakness and intellectual disability. METHODS: A clinical and histopathological characterisation of 25 Roma individuals with LGMD R18 caused by the homozygous TRAPPC11 c.1287+5G>A variant is reported. Functional effects of the variant on mitochondrial function were investigated. RESULTS: The c.1287+5G>A variant leads to a phenotype characterised by early onset muscle weakness, movement disorder, intellectual disability and elevated serum creatine kinase, which is similar to other series. As novel clinical findings, we found that microcephaly is almost universal and that infections in the first years of life seem to act as triggers for a psychomotor regression and onset of seizures in several individuals with TRAPPC11 variants, who showed pseudometabolic crises triggered by infections. Our functional studies expanded the role of TRAPPC11 deficiency in mitochondrial function, as a decreased mitochondrial ATP production capacity and alterations in the mitochondrial network architecture were detected. CONCLUSION: We provide a comprehensive phenotypic characterisation of the pathogenic variant TRAPPC11 c.1287+5G>A, which is founder in the Roma population. Our observations indicate that some typical features of golgipathies, such as microcephaly and clinical decompensation associated with infections, are prevalent in individuals with LGMD R18.
Asunto(s)
Discapacidad Intelectual , Microcefalia , Distrofia Muscular de Cinturas , Distrofias Musculares , Romaní , Humanos , Romaní/genética , Fenotipo , Distrofia Muscular de Cinturas/genética , Debilidad Muscular , Proteínas de Transporte VesicularRESUMEN
INTRODUCTION: Clinical Practice Guidelines have been shown to be valuable tools for guiding medical decisions. However, their mere publication has not reduced the variability of practice in terms of the way acute bronchiolitis is managed. METHOD: A before-and-after study design was used to analyse the effectiveness of a method of disseminating diagnostic recommendations among physicians regarding the management of infants, hospitalised due to bronchiolitis. Patients with comorbidities, ex-premature patients, and patients transferred to other hospitals were excluded. The diagnostic resources studied were: chest X-ray, full blood count, C-reactive protein, blood culture, venous blood gas, and determination of the respiratory syncytial virus. Eleven epidemic periods were analysed. RESULTS: A total of 259 patients were studied including 98 in the pre-intervention group (2006-2010), and 131 in the post-intervention group (2011-2017). The intervention took place in October of 2010 and 2011. A comparison of the two periods showed that the use of chest X-rays dropped from 73.5% to 16% (p<.01), full blood counts from 51% to 21.4% (p<.01), C-reactive protein from 48% to 22.1% (p<.01), and blood cultures from 23.5% to 7.6% (p<.01). Length of stay dropped by 0.6 (SD: 1) days and there were no differences in re-admission rates. CONCLUSIONS: The organised and systematised dissemination, using a multimodal method, of the diagnostic recommendations contained in the clinical practice guidelines on bronchiolitis, is capable of transforming the clinical practice by reducing the use of diagnostic resources, without an increase in the re-admission rate.
