Moody Kelly (summerlotion94)

Late-onset Pompe disease (LOPD) is an inherited autosomal recessive progressive metabolic myopathy that presents in the first year of life to adulthood. Clinical presentation is heterogeneous, differential diagnosis is challenging, and diagnostic delay is common. One challenge to differential diagnosis is the overlap of clinical features with those encountered in other forms of acquired/hereditary myopathy. Tongue weakness and imaging abnormalities are increasingly recognized in LOPD. In order to explore the diagnostic potential of tongue involvement in LOPD, we assessed tongue structure and function in 70 subjects, including 10 with LOPD naive to treatment, 30 with other acquired/hereditary myopathy, and 30 controls with neuropathy. Tongue strength was assessed with both manual and quantitative muscle testing. Ultrasound (US) was used to assess tongue overall appearance, echointensity, and thickness. Differences in tongue strength, qualitative appearance, echointensity, and thickness between LOPD subjects and neuropathic controls were statistically significant. Greater tongue involvement was observed in LOPD subjects compared to those with other acquired/hereditary myopathies, based on statistically significant decreases in quantitative tongue strength and sonographic muscle thickness. These findings provide additional evidence for tongue involvement in LOPD characterized by weakness and sonographic abnormalities suggestive of fibrofatty replacement and atrophy. Findings of quantitative tongue weakness and/or atrophy may aid differentiation of LOPD from other acquired/hereditary myopathies. Additionally, our experiences in this study reveal US to be an effective, efficient imaging modality to allow quantitative assessment of the lingual musculature at the point of care.Dravet syndrome is a well-established electro-clinical condition first described in 1978. A main genetic cause was identified with the discovery of a loss-of-function SCN1A variant in 2001. Mechanisms underlying the phenotypic variations have subsequently been a main topic of research. Various genetic modifiers of clinical severities have been elucidated through many rigorous studies on genotype-phenotype correlations and the recent advances in next generation sequencing technology. Furthermore, a deeper understanding of the regulation of gene expression and remarkable progress on genome-editing technology using the CRISPR-Cas9 system provide significant opportunities to overcome hurdles of gene therapy, such as enhancing NaV1.1 expression. This article reviews the current understanding of genetic pathology and the status of research toward the development of gene therapy for Dravet syndrome. This article is part of the Special Issue "Severe Infantile Epilepsies". Over the last decades aggressive interventions have been successful to improve nutritional outcomes in people with cystic fibrosis (CF). As a result, with improvement of life expectancy and new CFTR modulators, overweight and obesity are progressively becoming a source of concern for adult population and in developed countries. This was a multicenter, observational, cross-sectional study of 321 adults with CF at three large CF centers in Italy. Patients were divided into three groups according to BMI classes, overweight and obesity (OW) group including patients with BMI ≥25kg/m , normal weight (NW) group with BMI 18.6-24.9kg/m and underweight (UW) group with BMI ≤18.5kg/m . We demonstrated that prevalence of OW in adults with CF in Italy is 22%. OW status is independently associated with male sex (OR 3.520, P=0.001), pancreatic sufficiency (OR 2.873, P=0.014) and older age at diagnosis (1.015, P=0.042). BMI correlated with ppFEV1 (r=0.337; P<0.0001) with median ppFEV1 significantly higher in patients with OW than comparisons. We also reported preliminary data on unfavorable cardiovascular risk factors in a subgroup of patients, where median blood le