scholarly journals Targeted Therapies for Metabolic Myopathies Related to Glycogen Storage and Lipid Metabolism: a Systematic Review and Steps Towards a ‘Treatabolome’

2021 ◽  
pp. 1-18
Author(s):  
A. Manta ◽  
S. Spendiff ◽  
H. Lochmüller ◽  
R. Thompson
Keyword(s):  
Systematic Review ◽  
Lipid Metabolism ◽  
Genetic Defect ◽  
Genetic Mutation ◽  
Glycogen Storage ◽  
Carnitine Deficiency ◽  
Exercise Intolerance ◽  
Enzyme Replacement ◽  
Metabolic Myopathies ◽  
Published Evidence

Background: Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and β-oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking. Objective: The objective of this study was to collate all published evidence on pharmacological therapies for the aforementioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the “treatabolome” project. Methods: A systematic literature review was conducted to retrieve all levels of evidence examining the therapeutic efficacy of pharmacological treatments on metabolic myopathies related to glycogen storage and lipid metabolism. A key inclusion criterion was the availability of the genetic variant of the treated patients in order to link treatment outcome with the genetic defect. Results: Of the 1,085 articles initially identified, 268 full-text articles were assessed for eligibility, of which 87 were carried over into the final data extraction. The most studied metabolic myopathies were Pompe disease (45 articles), multiple acyl-CoA dehydrogenase deficiency related to mutations in the ETFDH gene (15 articles) and systemic primary carnitine deficiency (8 articles). The most studied therapeutic management strategies for these diseases were enzyme replacement therapy, riboflavin, and carnitine supplementation, respectively. Conclusions: This systematic review provides evidence for treatments of metabolic myopathies linked with the genetic defect in a computationally accessible format suitable for databasing in the treatabolome system, which will enable clinicians to acquire evidence on appropriate therapeutic options for their patient at the time of diagnosis.

Metabolic myopathies

2018 ◽  
Author(s):  
James B. Lilleker ◽  
Mark E. Roberts
Keyword(s):  
Muscle Pain ◽  
Clinical Presentation ◽  
Exercise Intolerance ◽  
Dietary Manipulation ◽  
Metabolic Myopathy ◽  
Treatment Resistant ◽  
Muscle Disorders ◽  
Enzyme Replacement ◽  
Metabolic Myopathies ◽  
Genetic Technologies

Metabolic myopathies are caused by defects in the metabolic processes of energy storage and utilization, and can present with exercise intolerance, fatigue, muscle pain, and weakness. Metabolic myopathies are rare and can be difficult to diagnose. However, the clinical presentation can be similar to, and thus mimic, both the idiopathic inflammatory myopathies and other genetic muscle disorders including the muscular dystrophies. Careful enquiry about the nature and timing of muscle pain, as well as identification of other clinical ‘red-flags’, can highlight the possibility of a metabolic myopathy. The possibility of metabolic myopathy or muscular dystrophy mimicking myositis should be considered early in ‘treatment-resistant myositis’ or ‘seronegative myositis’. The diagnosis of metabolic myopathies depends on a multidisciplinary team, an awareness of the increasing availability of enzyme activity testing and the utility of expanding genetic technologies. In some cases, dietary manipulation and enzyme replacement therapies are useful treatments.

Metabolic myopathies: a practical approach

2017 ◽  
Vol 18 (1) ◽  
pp. 14-26 ◽  
Author(s):  
James B Lilleker ◽  
Yann Shern Keh ◽  
Federico Roncaroli ◽  
Reena Sharma ◽  
Mark Roberts
Keyword(s):  
Genetic Disorders ◽  
Exercise Intolerance ◽  
Activity Measurement ◽  
Genetic Sequencing ◽  
Gene Therapies ◽  
Enzyme Replacement ◽  
Metabolic Myopathies ◽  
Recurrent Rhabdomyolysis ◽  
High Index Of Suspicion ◽  
Diagnostic Delays

Metabolic myopathies are a diverse group of rare genetic disorders and their associated muscle symptoms may be subtle. Patients may present with indolent myopathic features, exercise intolerance or recurrent rhabdomyolysis. Diagnostic delays are common and clinicians need a high index of suspicion to recognise and differentiate metabolic myopathies from other conditions that present in a similar fashion. Standard laboratory tests may be normal or non-specific, particularly between symptomatic episodes. Targeted enzyme activity measurement and next-generation genetic sequencing are increasingly used. There are now specific enzyme replacement therapies available, and other metabolic strategies and gene therapies are undergoing clinical trials. Here, we discuss our approach to the adult patient with suspected metabolic myopathy. We outline key features in the history and examination and discuss some mimics of metabolic myopathies. We highlight some disorders of glycogen and fatty acid utilisation that present in adulthood and outline current recommendations on management.

Characteristics of the Frequency-Following Response to Speech in Neonates and Potential Applicability in Clinical Practice: A Systematic Review

2020 ◽  
Vol 63 (5) ◽  
pp. 1618-1635
Author(s):  
Céline Richard ◽  
Mary Lauren Neel ◽  
Arnaud Jeanvoine ◽  
Sharon Mc Connell ◽  
Alison Gehred ◽  
...  
Keyword(s):  
Systematic Review ◽  
Cochrane Library ◽  
Neurodevelopmental Outcomes ◽  
Frequency Following Response ◽  
Ovid Medline ◽  
Published Evidence ◽  
Mesh Terms ◽  
Potential Applicability ◽  
Clinical Potential

Purpose We sought to critically analyze and evaluate published evidence regarding feasibility and clinical potential for predicting neurodevelopmental outcomes of the frequency-following responses (FFRs) to speech recordings in neonates (birth to 28 days). Method A systematic search of MeSH terms in the Cumulative Index to Nursing and Allied HealthLiterature, Embase, Google Scholar, Ovid Medline (R) and E-Pub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Web of Science, SCOPUS, COCHRANE Library, and ClinicalTrials.gov was performed. Manual review of all items identified in the search was performed by two independent reviewers. Articles were evaluated based on the level of methodological quality and evidence according to the RTI item bank. Results Seven articles met inclusion criteria. None of the included studies reported neurodevelopmental outcomes past 3 months of age. Quality of the evidence ranged from moderate to high. Protocol variations were frequent. Conclusions Based on this systematic review, the FFR to speech can capture both temporal and spectral acoustic features in neonates. It can accurately be recorded in a fast and easy manner at the infant's bedside. However, at this time, further studies are needed to identify and validate which FFR features could be incorporated as an addition to standard evaluation of infant sound processing evaluation in subcortico-cortical networks. This review identifies the need for further research focused on identifying specific features of the neonatal FFRs, those with predictive value for early childhood outcomes to help guide targeted early speech and hearing interventions.

scholarly journals mRNA therapy restores euglycemia and prevents liver tumors in murine model of glycogen storage disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jingsong Cao ◽  
Minjung Choi ◽  
Eleonora Guadagnin ◽  
Maud Soty ◽  
Marine Silva ◽  
...  
Keyword(s):  
Glycogen Storage Disease ◽  
Murine Model ◽  
Storage Disease ◽  
Liver Tumors ◽  
Glycogen Storage ◽  
Human Condition ◽  
Efficacy And Safety ◽  
Current Standard ◽  
Enzyme Replacement ◽  
Life Threatening

AbstractGlycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder caused by deficiency of glucose 6-phosphatase (G6Pase-α). G6Pase-α is critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) and carcinomas (HCCs). There is no treatment for GSD1a and the current standard-of-care for managing hypoglycemia (Glycosade®/modified cornstarch) fails to prevent HCA/HCC risk. Therapeutic modalities such as enzyme replacement therapy and gene therapy are not ideal options for patients due to challenges in drug-delivery, efficacy, and safety. To develop a new treatment for GSD1a capable of addressing both the life-threatening hypoglycemia and HCA/HCC risk, we encapsulated engineered mRNAs encoding human G6Pase-α in lipid nanoparticles. We demonstrate the efficacy and safety of our approach in a preclinical murine model that phenotypically resembles the human condition, thus presenting a potential therapy that could have a significant therapeutic impact on the treatment of GSD1a.

scholarly journals Workplace interventions that aim to improve employee health and well-being in male-dominated industries: a systematic review

2021 ◽  
pp. oemed-2020-107314
Author(s):  
Paige M Hulls ◽  
Rebecca C Richmond ◽  
Richard M Martin ◽  
Yanaina Chavez-Ugalde ◽  
Frank de Vocht
Keyword(s):  
Systematic Review ◽  
Mode Of Delivery ◽  
Well Being ◽  
Employee Health ◽  
Risk Of Bias ◽  
Workplace Health ◽  
Workplace Interventions ◽  
Published Evidence ◽  
Male Dominated ◽  
Health And Well Being

The published evidence on whether workplace health and well-being interventions are as effective in male-dominated industries compared with mixed-gender environments has not been synthesised. We performed a systematic review of workplace interventions aimed at improving employee health and well-being in male-dominated industries. We searched Web of Knowledge, PubMed, Medline, Cochrane Database and Web of Science for articles describing workplace interventions in male-dominated industries that address employee health and well-being. The primary outcome was to determine the effectiveness of the intervention and the process evaluation (intervention delivery and adherence). To assess the quality of evidence, Cochrane Collaboration’s Risk of Bias Tool was used. Due to the heterogeneity of reported outcomes, meta-analysis was performed for only some outcomes and a narrative synthesis with albatross plots was presented. After full-text screening, 35 studies met the eligibility criteria. Thirty-two studies delivered the intervention face-to-face, while two were delivered via internet and one using postal mail. Intervention adherence ranged from 50% to 97%, dependent on mode of delivery and industry. 17 studies were considered low risk of bias. Albatross plots indicated some evidence of positive associations, particularly for interventions focusing on musculoskeletal disorders. There was little evidence of intervention effect on body mass index and systolic or diastolic blood pressure. Limited to moderate evidence of beneficial effects was found for workplace health and well-being interventions conducted within male-dominated industries. Such interventions in the workplace can be effective, despite a different culture in male-dominated compared with mixed industries, but are dependent on delivery, industry and outcome. CRD42019161283.

The Dyslipidoses, Raúl Fleischmajer. Springfield, Thomas, 1960, 509 pp., $16.00

PEDIATRICS ◽  
1960 ◽  
Vol 26 (6) ◽  
pp. 914-914
Author(s):  
Benjamin H. Landing
Keyword(s):  
Fatty Acids ◽  
Lipid Metabolism ◽  
Glycogen Storage ◽  
General Survey ◽  
Storage Diseases ◽  
Glycogen Storage Diseases

This book begins with a general survey of the biochemistry and metabolism of fatty acids, glycerolipids, phospholipids, sphingolipids and cholesterol. A number of diseases involving "synthesis, transport or deposit" of these lipids are then reviewed, not including disorders of metabolism of steroids other than cholesterol, nor the carotenoids. The descriptions of clinical and pathologic aspects of the various diseases of lipid metabolism vary from good to excellent, and the author demonstrates both judgement and willingness to take a stand in some of the more controversial fields, such as the glycogen storage diseases.

Facial Nerve Dysfunction After Mandibular Distraction Osteogenesis in Patients with Robin Sequence: A Systematic Review and Meta-Analysis

2022 ◽  
pp. 105566562110707
Author(s):  
Elina Kapoor ◽  
Esperanza Mantilla-Rivas ◽  
Md Sohel Rana ◽  
Marudeen Aivaz ◽  
Daniela Duarte-Bateman ◽  
...  
Keyword(s):  
Systematic Review ◽  
Facial Nerve ◽  
Distraction Osteogenesis ◽  
Meta Analysis ◽  
Mandibular Distraction ◽  
Robin Sequence ◽  
Published Evidence ◽  
Mandibular Distraction Osteogenesis ◽  
Nerve Dysfunction ◽  
Distraction Rate

Objective Robin Sequence (RS), characterized by micrognathia, glossoptosis, and upper airway obstruction, is an increasingly recognized diagnosis. An effective surgical intervention is mandibular distraction osteogenesis (MDO). This study analyzes published evidence regarding facial nerve dysfunction (FND) associated with MDO. Design and Setting According to PRISMA guidelines, a systematic review was carried out with databases queried in June 2019 using MESH terms, or equivalent terms, as follows: “distraction osteogenesis” and “Robin Sequence”. A review of original Spanish and English articles, were included. Outcome measures included the prevalence of FND; the affected branches; the rate of permanent vs. transient FND; the use of an internal vs. external device; the daily distraction rate; and finally, the overall distraction length. Subsequently, a meta-analysis was conducted to collate results regarding the prevalence of FND and the factors associated with it. Results Of 239 unique studies identified, 19 studies with 729 patients met inclusion criteria; 52 patients developed FND after MDO. A random-effects meta-analysis yielded a pooled prevalence of FND of 6.40%, with moderately heterogeneous studies (I2 = 41%, τ2 = 0.006). Marginal mandibular nerve involvement was most commonly noted. Nine studies reported transient FND, six permanent, one both, and two unspecified. Internal distractors were used in 8 studies and external in 3 and both in 2. Distraction rate was 1.00 to 2.00 mm/day and total distraction length ranged from 13.00 to 22.3 mm. Sample size was the only parameter inversely associated with rate of FND (p = 0.04). Conclusion This analysis of FND associated with MDO for patients with RS demonstrates a lack of consistent documentation. MDO-associated FND does not appear to be uncommon, and permanent dysfunction can occur. This review underscores the importance of thorough documentation to elucidate the mechanism of FND.

scholarly journals Effect of ractopamine on lipid metabolism in vivo - a systematic review

2013 ◽  
Vol 56 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Matheus Soares da Silva Ferreira ◽  
Cesar Augusto Pospissil Garbossa ◽  
Guilherme Oberlender ◽  
Luciano José Pereira ◽  
Márcio Gilberto Zangeronimo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Lipid Metabolism
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