How are the metabolic myopathies diagnosed?
Once a detailed history and physical examination are performed, measurement of muscle enzymes and electrodiagnostic studies follow if complaints are suspicious for myopathy. Increased levels of CK, aldolase, liver transaminases, lactate dehydrogenase, carnitine, potassium, phosphorous, creatinine, lactate, ammonia, and myoglobin may be observed in the blood of patients depending on the metabolic myopathy. Of these, CK is the most sensitive. Levels are generally normal, except for patients with McArdle disease (myophosphorylase deficiency).
The EMG is useful in excluding a neuropathic process, demonstrating myopathic changes, and may delineate an optimal site for a muscle biopsy. Elevated muscle enzymes and myopathic changes on EMG are variable and nondiagnostic. A normal EMG does not exclude a metabolic myopathy. Measurement of venous lactate and ammonia during FET provides a useful tool for excluding all myopathic forms of GSD, except acid maltase deficiency, phosphorylase kinase b deficiency, and branching enzyme deficiency. A positive result can be confirmed by genetic testing or muscle biopsy enzyme analysis. A muscle biopsy can provide important diagnostic information in the evaluation of a patient with a metabolic muscle disease. Magnetic resonance spectroscopy is another tool useful for the in vivo evaluation of muscle energetics. Magnetic resonance imaging has been used to identify sites of abnormal tissue and as a guide for muscle biopsy.
Many metabolic myopathy specialists have moved to a genetic testing first approach. As the cost of genetic testing has plummeted and the speed of processing and sheer number of genes tested has increased; it is now more cost effective, faster, and less invasive to assess for the genetic defect prior to ancillary testing such as EMG, FET, or muscle biopsy. This inverted diagnostic stratagem still may require clinicians to circle back around to ancillary testing to help clarify variants of undetermined significance found on next generation sequencing panels, exomes, or genomes .
