Comparative skeletal muscle histopathologic and ultrastructural features in two forms of polysaccharide storage myopathy in horses

Polysaccharide storage myopathy (PSSM) has been found in more than 35 different horse breeds through identification of abnormal storage of polysaccharide in muscle biopsies. A dominant mutation in the glycogen synthase 1 gene (GYS1) accounts for a substantial proportion of PSSM cases in at least 17 breeds, including Quarter Horses, but some horses diagnosed with PSSM by muscle histopathologic analysis are negative for the mutation. We hypothesized that a second distinct form of glycogen storage disease exists in GYS1-negative horses with PSSM. The objectives of this study were to compare the histopathologic features, ultrastructure of polysaccharide, signalment, history, and presenting complaints of GYS1-negative Quarter Horses and related breeds with PSSM to those of GYS1-positive horses with PSSM. The total histopathologic score in frozen sections of skeletal muscle stained with hematoxylin and eosin, periodic acid Schiff (PAS) and amylase-PAS stains from 53 GYS1-negative horses did not differ from that of 52 GYS1-positive horses. Abnormal polysaccharide was fine granular or homogenous in appearance (49/53; 92%), often amylase-sensitive (28/53; 53%), more commonly located under the sarcolemma, and consisting of b glycogen particles in GYS1-negative horses. However, in GYS1-positive horses, abnormal polysaccharide was usually coarse granular (50/52; 96%), amylase-resistant (51/52; 98%), more commonly cytoplasmic, and consisting of b glycogen particles or, in some myofibers, filamentous material surrounded by b glycogen particles. Retrospective analysis found that GYS1-negative horses (n 5 43) were younger at presentation (4.9 6 0.6 years vs. 6.7 6 0.3 years for GYS1-positive horses) and were more likely to be intact males than GYS1-positive horses (n 5 160). We concluded that 2 forms of PSSM exist and often have distinctive abnormal polysaccharide. However, because evaluation of the histologic appearance of polysaccharide can be subjective and affected by age, the gold standard for diagnosis of PSSM at present would appear to be testing for the GYS1 mutation followed by evaluating muscle biopsy for characteristic abnormal polysaccharide in those horses that are negative for the mutation.