Discussion

Background: Type 1 PSSM is an autosomal dominant condition caused by a gain of function mutation (R309H) in skeletal muscle glycogen synthase (GYS1). Aims: To compare the effect of the R309H mutation on serum creatine kinase (CK) and aspartate aminotransferase (AST) activities in response to submaximal exercise. Methods: From a herd of adult Belgian and Percheron draught horses, 4 age, breed and sex-matched homozygotes (HH), heterozygotes (HR) and control horses (RR) were selected. The horses performed 20 min of submaximal exercise (trot and canter work) and blood samples were collected prior to, 4 h and 24 h post exercise for measurement of serum CK and AST activity. Results: Resting CK (P = 0.29) and AST (P = 0.20) activity was not significantly different between groups. There was no significant difference in post exercise AST activity between the groups at any time point (4 h P = 0.17, 24 h P = 0.13), whilst CK activity was significantly different between genotypes at 4 h (P = 0.04) but not 24 h (P = 0.06) post exercise. Post hoc analysis of CK activity at 4 h revealed a difference between homozygotes and controls (P<0.05), but there was considerable overlap between the heterozygotes and controls. Significant correlations between pre- and 24 h post exercise CK activity (r2 = 0.77, P<0.01), pre- and 4 h post exercise AST activity (r2 = 0.97, P<0.0001) and pre- and 24 h post exercise AST activity (r2 = 0.52, P<0.0001) were identified. Conclusions: Some individuals with PSSM1 have markedly increased muscle enzyme activities at rest and in response to a submaximal exercise test, particularly those with 2 copies of the R309H mutation. However, there is considerable overlap between responses in heterozygotes and controls. Practical significance: PSSM1 cannot be discounted on the basis of minimal increases in post exercise muscle enzyme activity.