Allele copy number and underlying pathology are associated with subclinical severity in equine type 1 polysaccharide storage myopathy (PSSM1).
Authors: Naylor Rosie J, Livesey Leanda, Schumacher John, Henke Nicole, Massey Claire, Brock Kenny V, Fernandez-Fuente Marta, Piercy Richard J
Journal: PloS one
Summary
# Editorial Summary: Allele Copy Number and Pathology in Equine PSSM1 Polysaccharide storage myopathy type 1 (PSSM1) affects a significant proportion of the equine population through a single founder mutation in the glycogen synthase gene, yet affected horses display remarkably variable clinical presentations—a discrepancy this 2012 study sought to explain by examining whether the severity of muscle pathology differs between homozygous and heterozygous carriers and correlates with clinical markers. Naylor and colleagues compared resting and post-exercise muscle enzyme activity (creatine kinase and aspartate aminotransferase) alongside histopathological assessment in homozygous, heterozygous and control horses, finding that homozygotes displayed significantly higher baseline CK (median 364 U/L versus 301 U/L in heterozygotes) and AST activity (mean 502 U/L versus 357 U/L), with AST showing strong correlation to the degree of subsarcolemmal vacuolation and cytoplasmic inclusion formation. The research identified incomplete dominance at the GYS1 locus—meaning heterozygotes express an intermediate phenotype—and demonstrated that the physical disruption to muscle fibres from glycogen and polysaccharide accumulation itself likely drives clinical signs, rather than simple metabolic dysfunction. For practitioners, this work clarifies why genetically identical mutations produce variable clinical presentations, supports the use of resting plasma enzyme activity as a subclinical severity marker, and suggests that management strategies minimising muscle damage alongside dietary modification may be particularly important in homozygous animals.
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Practical Takeaways
- •Homozygous PSSM1 horses are likely to have more severe clinical signs than heterozygotes; genetic testing for allele copy number helps predict disease severity and management needs
- •Resting plasma AST and CK levels serve as practical biomarkers for assessing underlying muscle pathology severity in PSSM1-affected horses
- •Understanding that physical disruption from polysaccharide accumulation drives symptoms supports management strategies focused on glycogen depletion through diet and exercise
Key Findings
- •Homozygous PSSM1 horses had significantly higher resting CK (364 U/L) and AST (502 U/L) activities compared to heterozygotes and controls, indicating dose-dependent gene expression
- •Resting plasma AST activity showed strong positive correlation with severity of subsarcolemmal vacuolation (rho=0.816, P=0.01) and cytoplasmic inclusions (rho=0.766, P=0.01)
- •PSSM1-affected horses demonstrated altered muscle fiber type composition with fewer type 2× and more type 2a fibers compared to controls
- •Physical disruption of muscle fibers from glycogen and polysaccharide accumulation may contribute to the myopathic phenotype severity