Size in Myotonic Dystrophy

Background Myotonic dystrophy, the most common form of adult dystrophy, has been shown to be caused by amplification of CTG triplet repeat in the 3' untranslated region of a protein kinase gene located on chromosome 19. Impaired glucose metabolism has been suggested as a possible explanation of brain and skeletal muscle involvement in this multisystem disease. We investigated whether myocardial glucose metabolism is impaired in myotonic dystrophy and whether this impairment is related to the size of the mutation. Methods and Results The myocardial metabolic rate for glucose (MMRGlu, ,mol * min'* g-'), Kl (blood-to-tissue transfer constant), k2 (tissue-to-blood transfer constant), and k3 (phosphorylation rate constant) were determined in 7 control subjects and 12 patients with myotonic dystrophy by using parametric images generated from dynamic cardiac positron emission tomography (PET) and '8F-fluoro-2-deoxyglucose studies. The expansion of the CTG triplet repeats was analyzed in patients with the probe cDNA25 after EcoRI digestion. Nonparametric tests were used to compare quantitative variables between control subjects and patients. The correlations between the size of the mutation and PET parameters were studied by linear regression. MMRGlu and k3 were significantly decreased in patients compared with control subjects (0.39±0.20 versus 0.64±0.25, P=.03, and 0.09±0.07 versus 0.24+0.21, P=.03, respectively), whereas Kl and k2 were not statistically different between control subjects and patients. MMRGlu and k3 correlate inversely with the length of the CTG triplet repeat (r= -.65 and P=.03 for MMRGlu, and r= -.85 and P=.001 for k3, respectively). Conclusions In myotonic dystrophy, the observed reductions in MMRGlu and phosphorylation are inversely linked to the length of the mutation. This observation suggests that impaired modulation of a protein kinase involved in myocardial hexokinase activation may give a pathophysiological schema to relate the molecular defect and the abnormal myocardial metabolism in myotonic dystrophy. (Circulation. 1994;90:2629-2634.)