Abstract

Metabolic myopathies (MM) are rare inherited primary muscle disorders that are mainly due to abnormalities of muscle energy metabolism resulting in skeletal muscle dysfunction. These diseases include disorders of fatty acid oxidation, glyco(geno)lytic muscle disorders and mitochondrial respiratory chain (MRC) disease. 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 ‘rhabdomyolysis’ 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 ‘rhabdomyolysis’ 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.