Evaluating efficacy of clinical tools in determining causes of recurrent rhabdomyolysis

Rhabdomyolysis is a poorly understood condition characterized by the rapid breakdown of skeletal muscle tissue. Recurrent episodes are very debilitating, and these patients often undergo extensive workup with no etiology identified. Maximal cycle exercise testing (CPX) provides numerical markers which when elevated can provide evidence of a peripheral limitation to exercise. Twenty-three patients with recurrent rhabdomyolysis episodes performed ramp cycle testing where they pedaled between 60-70 rpm at 2 sub-maximal and one maximal exercise state. Data collected included heart rate, blood pressure, oxygen saturation, oxygen consumption, and cardiac output. These patients’ files were also queried for EMG, DNA, or biopsy testing. Only 2 of 10 EMG studies showed myopathic studies, 1 of which was associated with an underlying myopathy. 20 muscle biopsies showed normal non-specific changes with only 1 indicating a possible underlying myopathy. Nuclear DNA testing only identified a definitive cause in 1 of 20 cases with an additional 12 showing variants of unknown significance in rhabdomyolysis associated genes. 4 patients had an elevated ratio of cardiac output to maximal oxygen consumption, all of which had positive mitochondrial DNA testing. CPX shows potential as a non-invasive method of identifying people at risk of recurrent rhabdomyolysis episodes before further testing. Further studies exploring the role of polygenic mutations in rhabdomyolysis would be beneficial.