Discussion
Naylor, R.J., Livesey, L., Schumacher, J., Luis-
Fuentes, V., Massey, C., Henke, N., Fernandez-
Fuente, M., †Brock, K. and Piercy, R.J.
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 preand
24 h post exercise CK activity (r2 = 0.77, P<0.01), pre- and
Friday 14th September n Hall 8B
Clinical Research
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.