Polysaccharide Storage Myopathy, Type 2

Type 1 Polysaccharide Storage Myopathy (PSSM) is caused by a mutation in the GYS1 gene. However, not all cases of PSSM diagnosed by muscle biopsy are caused by the GYS1 mutation. For example, 25% of PSSM cases in Quarter Horses are not due to the GYS1 mutation. Additionally, we have not found the GYS1 mutation in at least 18 breeds of horses previously reported to have PSSM. Therefore, our most recent research suggests that there are at least two forms of PSSM: Type 1, which is caused by the GYS1 mutation and Type 2, which is the term we are currently using for the yet to be identified cause of other PSSM cases. These two forms of PSSM are present in varying and largely unknown proportions in each breed of horse.

Many horses with Type 2 PSSM share many of the clinical signs of Type 1 PSSM, have excessive glycogen in their muscles, and respond to a low starch high fat diet and regular daily exercise. Similar to Type 1 PSSM, Type 2 PSSM also likely has a genetic basis; however the underlying genetic mutation has yet to be identified. Our current focus is finding the cause of Type 2 PSSM within the Quarter Horse breed by performing a whole genome association mapping with nuclear DNA markers to identify positional candidate genes. This is similar to the approach we used for Type 1 PSSM that was successful in identifying the GYS1 mutation.

This work is funded by American Quarter Horse Foundation “Genetic Analysis of Glycogen Storage Disorders in Quarter Horses” and NIH-NIAMS “Regulation of glycogen metabolism: Insights from novel genetic models”

McCue, ME, Armién, AG, Valberg, SJ, Lucio, M, Mickelson, JR. Comparative skeletal muscle histopathologic and ultrastructural features in two forms of Polysaccharide Storage Myopathy in horses. Vet Pathol. 2009 Nov;46(6):1281-91. PMID: 19605906.