Polysaccharide Storage Myopathy 1, PSSM1

 

Gene: GYS1

Transmission: Autosomal dominant (incomplete)

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  One or both of the parents of an animal with the mutation has one or two copies of the mutation.  Animals that have one or two copies of the mutation can pass the mutation on to future generations.

Mutation: Substitution, GYS1 gene; c.309 G>A, exon6

Medical systems: Muscular, metabolic

Breeds: Draft horses, warmbloods, Quarter Horse

Age of onset of symptoms: During physical effort

Polysaccharide Storage Myopathy 1 (PSSM1) is a genetic disease seen in draft horses, Warmbloods and in Quarter Horses.  The cause of PSSM1 is an enzyme mutation that disrupts the use and availability of glycogen as a short-term energy source in the muscles, resulting in the buildup of glycogen in the muscles of affected horses.  Clinical signs include exercise intolerance, muscle cramps and stretching, muscle pain that can be severe, myoglobinuria (myoglobin in the urine), to complete inability to get up.  In addition, the affected animal is unable to properly digest sugars from grain.

 

References:

Labgenvet blog

OMIA Link: [1158-9796]

Aleman M, Scalco, R, Malvick J, et al. (2022) Prevalence of genetic mutations in horses with muscle disease from a neuromuscular disease laboratory. J Equine Vet Sci 118:104129.  [pubmed/36150530]

Aldrich K, Belez-Irizarry D, Fenger C, et al. (2021) Pathways of calcium regulation, electron transport, and mitochondrial protein translation are molecular signatures of susceptibility to recurrent exertional rhabdomyosysis in Thoroughbred racehorses.  PLoS One 16: e0244556 [pubmed/33566847]

Tosi I, Art T, Cassart D, Farnir F, et al. (2018) Altered mitochondrial oxidative phosphorylation capacity in horses suffering from polysaccharide storage myopathy.  J Bioenerg Biomembr 50(5):379-390 [pubmed/30143916]

Lewis SS, Nicholson AM Williams ZJ, Valbert SJ. (2017) Clinical characteristics and muscle glycogen concentrations in warmblood horses with polysaccharide storage myopathy.  Am J Vet Res 78:1305-1312.  [pubmed/29076373]

Maile CA, Hingst JR, Mahalingan KK, et al. (2016) A highly prevalent equine glycogen storage disease is explained by constitutive activation of a mutant glycogen synthase.  Biochim Biophys Acta 1861(1PtA):3388-3398. [pubmed/27592162]

McCoy AM, Schaefer R, Petersen JL et al. (2014) Evidence of positive selection for a glycogen synthase (GYS1) mutation in domestic horse populations. J Hered. 105(2):163-72. [pubmed/24215078]

McCue ME, Anderson SM, Valberg SJ, et al. (2010) Estimated prevalence of the Type 1 Polysaccharide Storage Myopathy mutation in selected North American and European breeds. Anim Genet. 41 Suppl 2:145-149. [pubmed/21070288]

McCue ME, Valberg SJ, Jackson M, et al. (2009) Polysaccharide Storage Myopathy Phenotype in Quarter Horse-Related Breeds Is Modified by the Presence of an RYR1 Mutation. Neuromuscul Disord. 19(1):37-43. [pubmed/19056269]

McCue ME, Valberg SJ, Miller MB, et al. (2008) Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis. Genomics. 91(5):458-466. [pubmed/18358695]