Test Detail

Polysaccharide storage myopathy type 1 (PSSM1) is an inherited muscle glycogenosis of the horse, caused by a mutation in the GYS1 gene that keeps glycogen synthase permanently active. The muscle accumulates glycogen and abnormal polysaccharide in excess and becomes prone to episodes of rhabdomyolysis (tying-up) with stiffness, pain and dark urine. It affects Quarter Horses, stock breeds, draft breeds and many other equine populations. It is manageable with diet and exercise management, and DNA testing distinguishes PSSM1 from other myopathies, including PSSM2.

Breeds with the variant documented in OMIA001158-9796: Quarter Horse, American Paint, Appaloosa, Belgian Draft, Haflinger and Noric, as well as other draft and cold-blood breeds described in the literature (e.g. Cob Normand, PMID:18822097). Carrier frequencies vary by breed and country and are not consolidated in unsampled populations. Being a dominant variant, a single positive breeding animal can spread the allele rapidly.

- Episodes of muscle stiffness and pain (tying-up), especially after rest and resumption of exercise\n- Stiff gait, reluctance to move, sweating and trembling of the hindquarters\n- Dark urine (myoglobinuria) in overt rhabdomyolysis\n- Marked elevations of CK and AST on bloodwork\n- Some horses show only poor performance or abnormal gait without an acute crisis\n- Severe episodes with recumbency and secondary renal failure due to myoglobinuria

PSSM was characterised in the early 1990s in Quarter Horses with recurrent episodes of rhabdomyolysis and muscle deposits of abnormal polysaccharide on biopsy. Its genetic basis was unknown until 2008, when the group of McCue and Valberg identified the R309H mutation of the GYS1 gene, which explains the PSSM1 form. Shortly afterwards it was found that a proportion of horses with a compatible biopsy have normal GYS1 (a group termed PSSM2), which is heterogeneous and under investigation. GYS1 testing became widespread in breed associations and is today one of the most requested myopathy tests in the species.

- Test breeding animals of stock and draft breeds before the breeding season\n- Being dominant, every P1 animal transmits the allele to 50% of its offspring: breed preferably with N/N\n- Never mate P1 with P1: 25% risk of homozygotes with more severe presentations\n- A P1 with exceptional genetic value can be mated to N/N, but avoid chaining generations of positives\n- Do not use the test alone: an N/N may have PSSM2 or another myopathy; if symptoms appear, complete the study with a biopsy

Differential diagnosis of rhabdomyolysis: PSSM2, atypical myopathy (hypoglycin A from maple seeds), HYPP, vitamin deficiencies, infectious and traumatic myopathies. PSSM1 is confirmed by the GYS1 test; biopsy shows PAS-positive deposits resistant to diastase. Management is highly effective: a low-starch, high-fat diet, daily and regular exercise avoiding prolonged rest with feed, and split meals. Serial CK/AST guide the response to the plan.

1. Valberg SJ, Cardinet GH 3rd, Carlson GP, DiMauro S. Polysaccharide storage myopathy associated with recurrent exertional rhabdomyolysis in horses. Neuromuscul Disord 1992. PMID:1284408.
2. Valberg SJ, Geyer C, Sorum SA, Cardinet GH 3rd. Familial basis of exertional rhabdomyolysis in quarter horse-related breeds. Am J Vet Res 1996. PMID:8669756.
3. McCue ME, Valberg SJ, Miller MB, Wade C, et al. Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis. Genomics 2008. PMID:18358695.
4. McCue ME, Valberg SJ, Lucio M, Mickelson JR. Glycogen synthase 1 (GYS1) mutation in diverse breeds with polysaccharide storage myopathy. J Vet Intern Med 2008. PMID:18691366.
5. Herszberg B, McCue ME, Larcher T, Mata X, et al. A GYS1 gene mutation is highly associated with polysaccharide storage myopathy in Cob Normand draught horses. Anim Genet 2009. PMID:18822097.