Comparative skeletal muscle histopathologic and ultrastructural features in two forms of polysaccharide storage myopathy in horses.
Authors: McCue M E, Armién A G, Lucio M, Mickelson J R, Valberg S J
Journal: Veterinary pathology
Summary
Polysaccharide storage myopathy (PSSM) affects horses across numerous breeds, but whilst a dominant GYS1 gene mutation explains many cases, some horses show typical histopathologic features without carrying this mutation, suggesting an alternative form of the disease exists. McCue and colleagues examined muscle biopsies from 53 GYS1-negative and 52 GYS1-positive horses using light microscopy and electron microscopy to characterise the structural differences between these two groups. The hallmark distinction lay in polysaccharide morphology: GYS1-negative horses displayed fine granular or homogenous deposits that were predominantly subsarcolemmal and frequently amylase-sensitive (92% and 53% respectively), whilst GYS1-positive horses showed coarse granular, amylase-resistant, cytoplasmic accumulation in 96% and 98% of cases. Additionally, GYS1-negative horses presented at a younger average age (4.9 versus 6.7 years) and were predominantly intact males, adding a clinical distinction to the molecular and ultrastructural differences. For practitioners, this research clarifies that genetic testing for GYS1 mutations should be the first diagnostic step, with muscle biopsy reserved for mutation-negative horses where the characteristic fine granular, subsarcolemmal polysaccharide pattern would then confirm the diagnosis of PSSM type 2—enabling appropriate management strategies tailored to the underlying metabolic defect.
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Practical Takeaways
- •Do not rely on muscle biopsy appearance alone to diagnose PSSM—genetic testing for GYS1 mutation must be performed first, followed by biopsy only if mutation-negative
- •Young intact males presenting with myopathy symptoms may have GYS1-negative PSSM and warrant genetic screening
- •Understanding the two forms of PSSM helps guide appropriate management and breeding decisions, as they have different underlying genetic causes
Key Findings
- •Two distinct forms of PSSM exist with different histopathologic and ultrastructural features: GYS1-negative horses show fine granular/homogenous, amylase-sensitive polysaccharide under the sarcolemma, while GYS1-positive horses show coarse granular, amylase-resistant cytoplasmic polysaccharide
- •GYS1-negative horses presented at younger age (4.9 years) compared to GYS1-positive horses (6.7 years)
- •GYS1-negative horses were more likely to be intact males than GYS1-positive horses
- •Overall histopathologic scores did not differ between the two forms, making genetic testing essential for definitive diagnosis