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Alternative Title
Abstract
Background: Lipid storage myopathy (LSM) is a diverse group of lipid metabolic disorders with great variations in the clinical phenotype and age of onset. Classical multiple acyl-CoA dehydrogenase deficiency (MADD) is known to occur secondary to mutations in electron transfer flavoprotein dehydrogenase (ETFDH) gene. Whole exome sequencing (WES) with clinical correlations can be useful in identifying genomic alterations for targeted therapy. Case presentation: We report a patient presented with severe muscle weakness and exercise intolerance, suggestive of LSM. Diagnostic testing demonstrated lipid accumulation in muscle fibres and elevated plasma acyl carnitine levels. Exome sequencing of the proband and two of his unaffected siblings revealed compound heterozygous mutations, c.250G > A (p.Ala84Thr) and c.770A > G (p.Tyr257Cys) in the ETFDH gene as the probable causative mutations. In addition, a previously unreported variant c.1042C > T (p.Arg348Trp) in ACOT11 gene was found. This missense variant was predicted to be deleterious but its association with lipid storage in muscle is unclear. The diagnosis of MADD was established and the patient was treated with riboflavin which resulted in rapid clinical and biochemical improvement. Conclusions: Our findings support the role of WES as an effective tool in the diagnosis of highly heterogeneous disease and this has important implications in the therapeutic strategy of LSM treatment. © 2018 The Author(s).
Keywords
acyl coenzyme A dehydrogenase, acylcarnitine, creatine kinase, riboflavin, steroid, electron transferring flavoprotein, electron-transferring-flavoprotein dehydrogenase, iron sulfur protein, oxidoreductase, riboflavin, aged, alcohol consumption, Article, case report, clinical article, creatinine blood level, diagnostic test, diet therapy, disease association, disease severity, dysphagia, ETFDH gene, exercise, family history, gene, gene mutation, genetic screening, genetic variability, histopathology, human, lipid blood level, lipid storage, lipidosis, low fat diet, male, multiple acyl CoA dehydrogenase deficiency, muscle biopsy, muscle strength, muscle weakness, non insulin dependent diabetes mellitus, priority journal, vitamin blood level, whole exome sequencing, adolescent, adult, female, genetics, heterozygote, middle aged, multiple acyl CoA dehydrogenase deficiency, mutation, pedigree, Adolescent, Adult, Electron-Transferring Flavoproteins, Female, Heterozygote, Humans, Iron-Sulfur Proteins, Male, Middle Aged, Multiple Acyl Coenzyme A Dehydrogenase Deficiency, Mutation, Oxidoreductases Acting on CH-NH Group Donors, Pedigree, Riboflavin
Source Title
BMC Medical Genomics
Publisher
BioMed Central Ltd.
Series/Report No.
Collections
Rights
Date
2018
DOI
10.1186/s12920-018-0356-8
Type
Article