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Clinically these disorders present with a range of symptoms including infantile hypotonia, myalgia\/exercise tolerance, chronic or acute muscle weakness, cramps\/spasms\/stiffness or episodic acute rhabdomyolysis. The precipitant may be fasting, infection, general anaesthesia, heat\/cold or most commonly, exercise. However, the differential diagnosis includes a wide range of both acquired and inherited conditions and these include exposure to drugs\/toxins, inflammatory myopathies, dystrophies and channelopathies. Streamlining of existing diagnostic protocols has now become a realistic prospect given the availability of second-generation sequencing. A diagnostic pathway using a \u2018rhabdomyolysis\u2019 gene panel at an early stage of the diagnostic process is proposed. Following detailed clinical evaluation and first-line investigations, some patients will be identified as candidates for McArdle disease\/glycogen storage disease type V or MRC disease and these will be referred directly to the specialised services. However, for the majority of patients, second-line investigation is best undertaken through next-generation sequencing using a \u2018rhabdomyolysis\u2019 gene panel. Following molecular analysis and careful evaluation of the findings, some patients will receive a clear diagnosis. Further functional or specific targeted testing may be required in other patients to evaluate the significance of uncertain\/equivocal findings. For patients with no clear diagnosis, further investigations will be required through a specialist centre.<\/jats:p>","DOI":"10.1136\/jclinpath-2014-202808","type":"journal-article","created":{"date-parts":[[2015,4,15]],"date-time":"2015-04-15T23:26:24Z","timestamp":1429140384000},"page":"410-417","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["The investigation and management of metabolic myopathies"],"prefix":"10.1136","volume":"68","author":[{"given":"Simon Edward","family":"Olpin","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry, Sheffield Children's NHS Foundation Trust, Sheffield, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Murphy","sequence":"additional","affiliation":[{"name":"Charles Dent Metabolic Unit, The National Hospital for Neurology & Neurosurgery, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard 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