A glycogen synthase 1 mutation associated with equine polysaccharide storage myopathy and exertional rhabdomyolysis occurs in a variety of UK breeds.
Authors: Stanley R L, McCue M E, Valberg S J, Mickelson J R, Mayhew I G, McGowan C, Hahn C N, Patterson-Kane J C, Piercy R J
Journal: Equine veterinary journal
Summary
# Editorial Summary: GYS1 Mutation and Polysaccharide Storage Myopathy in UK Horses The R309H glycogen synthase 1 (GYS1) mutation, previously documented in American horses with polysaccharide storage myopathy (PSSM), had not been characterised in the UK population until this investigation. Researchers genotyped 47 UK horses presenting with exertional rhabdomyolysis and pursued muscle biopsy diagnosis, alongside screening 37 additional cases with histopathologically confirmed grade 2 PSSM. The mutation was identified in 10 of 47 rhabdomyolysis cases (21%) and notably in 24 of 37 grade 2 PSSM cases (65%), but was absent from horses with normal muscle architecture or grade 1 PSSM—establishing a clear genotype-phenotype association. Beyond the expected Quarter Horse and Appaloosa breeds, the mutation was found across Warmbloods, Connemaras, Cobs, Polo Ponies and Thoroughbred crosses, indicating the condition's broader relevance to diverse UK bloodlines. Whilst the GYS1 mutation represents a significant proportion of exertional myopathy in British horses, the authors emphasise that genetic screening should complement rather than replace muscle biopsy, as a substantial number of affected horses harbour alternative disease aetiologies—making diagnostic interpretation nuanced and requiring clinicians to avoid over-reliance on a single genetic test.
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Practical Takeaways
- •Consider GYS1 genotyping in UK horses presenting with exertional rhabdomyolysis, particularly before or alongside muscle biopsy, as it identifies a significant proportion of cases (21% in this cohort)
- •Grade 2 PSSM cases (amylase-resistant polysaccharide accumulation) have a much higher likelihood of carrying the GYS1 mutation (65%) and should be prioritized for genetic testing
- •Be aware that a negative GYS1 result does not rule out PSSM or exertional rhabdomyolysis—alternative diagnoses must still be considered and investigated in symptomatic horses
Key Findings
- •The R309H GYS1 mutation was found in 10/47 (21%) UK horses with exertional rhabdomyolysis undergoing muscle biopsy
- •The mutation was present in 24/37 (65%) of grade 2 PSSM cases but absent in normal biopsies and grade 1 PSSM cases
- •Multiple UK breeds carried the mutation including Quarter Horse, Appaloosa, Warmblood, Connemara-cross, Cob, Polo Pony and Thoroughbred cross
- •GYS1 mutation is an important cause of exertional rhabdomyolysis in UK horses but does not account for all PSSM cases