Alpha-sarcoglycanopathy presenting as exercise intolerance and rhabdomyolysis in two adults

• DOI: 10.1016/j.nmd.2015.09.010
• Publication Date: 2015-09-25T21:57:49Z
• Authors: M. Tarnopolsky; E. Hoffman; M. Giri; J. Shoffner; L. Brady
• Keywords: Adult; Male; Exercise Tolerance; Myalgia; Rhabdomyolysis; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Sarcoglycans; Sarcoglycanopathies; Humans; Female; Muscle, Skeletal

Two patients with exercise-induced myalgias and rhabdomyolysis with myoglobinuria were evaluated with muscle biopsy and comprehensive myopathy next generation sequencing (NGS) gene panels. Genetic analysis revealed homozygosity for two known pathogenic SGCA mutations (R284C in Patient 1 and V247M in Patient 2). Muscle biopsy showed minimal changes with normal immunohistochemistry for α-sarcoglycan. Western blotting showed 27% and 35% of normal α-sarcoglycan immunoreactivity when compared to age matched controls, confirming the diagnosis of α-sarcoglycanopathy in both patients. The sarcoglycan genes should be added to the differential diagnosis for cases that present with rhabdomyolysis, exercise intolerance, and hyperCKemia, even in the absence of muscle weakness or normal α-sarcoglycan immunohistochemistry. Work-up of patients with these types of non-specific presentation may be best facilitated through the use of non-specific NGS myopathy panels.