Polysaccharide Storage Myopathy (PSSM1)

Quick Summary

Type 1 Polysaccharide Storage Myopathy is a glycogen storage disease that results in the accumulation of abnormal complex sugars in muscle cells, which can lead to muscle pain, weakness, and reluctance to move.

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Phenotype: Horses with Type 1 Polysaccharide Storage Myopathy (PSSM1) have a muscle disease characterized by accumulation of abnormal complex sugars (glycogen) in skeletal muscles. The accumulation of abnormal sugars can cause breakdown of muscle fibers (rhabdomyolosis) which leads to muscle pain, weakness, skin twitching, sweating, and reluctance to move.

Mode of Inheritance: Autosomal dominant

Alleles: N = Normal, PSSM1 = Polysaccharide Storage Myopathy Type I

Breeds appropriate for testing: Quarter Horses and related breeds including Paint Horses, Appaloosas, and Pony of the Americas. Draft Horse breeds including Belgian, Percheron, Shire, Haflinger, and Cob Normand draught horses. Additional breeds include Exmoor Ponies, Morgan, Mustang, Noriker, Rhenish German Coldblood, Rocky Mountain Horse, Tennessee Walking Horse, Saxon-Thuringian Coldbloods, South German Coldbloods, and various Warmblood breeds.

Explanation of Results:

  • Horses with N/N genotype will not have type 1 Polysaccharide Storage Myopathy and cannot transmit the PSSM1 variant to their offspring.
  • Horses with N/PSSM1 genotype will have the PSSM1 variant and may show signs of type 1 disease. Horses with this genotype may transmit the PSSM1 variant to 50% of their offspring.
  • Horses with PSSM1/PSSM1 genotype are homozygous for the PSSM1 variant and may be more severely affected than N/PSSM1 horses. Horses with this genotype will transmit the PSSM1 variant to all of their offspring.

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Turnaround Time
At least 15 business days; may be delayed beyond 15 business days if sample requires additional testing, or a new sample is requested.
Additional Details

Type 1 Polysaccharide Storage disease (PSSM1) is a potentially life-threatening glycogen storage disease (glycogenosis) that affects skeletal muscles. The disease results from the accumulation of abnormal glycogen (carbohydrate storage molecule) that can damage muscle cells. Abnormal accumulation of glycogen was historically diagnosed by taking a muscle biopsy and determining if glycogen in the muscle was resistant to digestion with an enzyme known as amylase. Horses with PSSM1 show clinical signs that range from muscle soreness and weakness to muscle atrophy and acute exertional rhabdomyolysis (breakdown of muscle fibers) which can result in the reluctance of a horse to move.

Research at the University of Minnesota by Drs. McCue, Valberg, Mickelson, and colleagues identified the causal mutation for PSSM1. A single base substitution in the glycogen synthase 1 gene (GYS1) results in a change in the protein that replaces the normal arginine with histidine at amino acid number 309 (denoted as p.309Arg>His or p.R309H). The normal protein functions in skeletal muscle cells to convert excess glucose to a normal glycogen. This glycogen is stored and later converted back to glucose when the muscle cell needs energy to function. When histidine is present instead of the normal arginine, the protein activity is higher and results in an excess of glycogen that is not properly made (less branched structure). Because this glycogen is not properly branched, the conversion of this storage molecule to an energy source muscle cells can readily use is hindered, thus causing damage to the muscle upon exercise.

PSSM1 is inherited as an autosomal dominant trait, which means a single copy of the PSSM1 variant can cause symptoms of disease. However, a study in 2012 by Naylor and colleagues, investigating genotype for PSSM1, histopathology, and enzyme function provided evidence that homozygotes may be more severely affected. Specifically, homozygotes tended to have more severe histopathological changes and more amylase-resistant polysaccharide inclusions (abnormal glycogen) particularly in type 2A fibers than heterozygotes. Another study published in 2009 by McCue and colleagues reported more severe clinical phenotypes of PSSM1 in horses with malignant hyperthermia (MH). MH is also inherited as an autosomal dominant trait and is caused by a mutation in another gene known as the ryanodine receptor 1 (RYR1). These findings illustrate the importance of utilizing results from both genetic tests in clinical diagnosis and management of disease. 

The PSSM1 variant has been documented in at least 30 horse breeds and has been observed to range in frequency among these breeds. The prevalence is reported to be highest in some draft horse breeds and lowest in warmblood breeds. The PSSM1 variant is believed to be an old mutation that may have been under positive selection in some draft breeds, particularly the Belgian horse. This mutation may have been advantageous to horses that had daily work schedules with limited sugar feed intake.

Testing for PSSM1 can help to inform clinical, management, and breeding decisions. If a horse tests positive for the PSSM1 variant, veterinarians should be consulted to develop a diet and exercise regime that best manages the disease.

It is important to note, however, that the PSSM1 variant does not explain all cases of excessive abnormal glycogen accumulation in the muscle. It is likely that other genetic factors contribute to this condition, but to date no genetic variants for other types of PSSM (for example, PSSM type 2) have been identified or scientifically validated.

Type of Sample

Species

Type of Test

Results Reported As
Test Result Polysaccharide Storage Myopathy (PSSM1)
N/N Normal - horse does not have the PSSM1 gene.
N/PSSM1 Affected - horse has one copy of the PSSM1 gene.
PSSM1/PSSM1 Affected - horse has two copies of the PSSM1 gene.
References

McCue, M.E., Valberg, S.J., Miller, M.B., Wade, C., DiMauro, S., Akman, H.O., & Mickelson, J.R. (2008). Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis. Genomics, 91(5), 458-466. doi: 10.1016/j.ygeno.2008.01.011

McCue, M.E., Valberg, S.J., Lucio, M., & Mickelson, J.R. (2008). Glycogen synthase 1 (GYS1) mutation in diverse breeds with polysaccharide storage myopathy. Journal of Veterinary Internal Medicine, 22(5), 1228-1233. doi: 10.1111/j.1939-1676.2008.0167.x

Herszberg, B., McCue, M.E., Larcher, T., Mata, X., Vaiman, A., Chaffaux, S., Cherel, Y., Valberg, S.J., Mickelson, J.R., & Guerin, G. (2009). A GYS1 gene mutation is highly associated with polysaccharide storage myopathy in Cob Normand draught horses. Animal Genetics, 40(1), 94-96. doi: 10.1111/j.1365-2052.2008.01778.x

McCue, M E et al. “Polysaccharide storage myopathy phenotype in quarter horse-related breeds is modified by the presence of an RYR1 mutation.” Neuromuscular disorders : NMD vol. 19,1 (2009): 37-43. doi:10.1016/j.nmd.2008.10.001

McCue, M.E., Anderson, S.M., Valberg, S.J., Piercy, R.J., Barakzai, S.Z., Binns, M.M., Distl, O., Penedo, M.C., Wagner, M.L., & Mickelson, J.R. (2010). Estimated prevalence of the Type 1 Polysaccharide Storage Myopathy mutation in selected North American and European breeds. Animal Genetics, 41(Suppl 2), 145-149. doi: 10.1111/j.1365-2052.2010.02124.x

Naylor, R.J., Livesey, L., Schumacher, J., Henke, N., Massey, C., Brock, K.V., Fernandez-Fuente, M., & Piercy, R.J. (2012). Allele copy number and underlying pathology are associated with subclinical severity in equine type 1 polysaccharide storage myopathy (PSSM1). PloS One, 7(7), e42317. doi: 10.1371/journal.pone.0042317

McCoy, A.M., Schaefer, R., Petersen, J.L., Morrell, P.L., Slamka, M.A., Mickelson, J.R., Valberg, S.J., & McCue, M.E. (2014). Evidence of positive selection for a glycogen synthase (GYS1) mutation in domestic horse populations. Journal of Heredity, 105(2), 163-172. doi: 10.1093/jhered/est075

Druml, T., Grilz-Seger, G., Neuditschko, M., & Brem, G. (2017). Association between population structure and allele frequencies of the glycogen synthase 1 mutation in the Austrian Noriker draft horse. Animal Genetics, 48(1), 108-112. doi: 10.1111/age.12481

License Info

This test is performed under a license agreement with Equine LLC and the American Quarter Horse Association.