CORRELATION BETWEEN DECREASED MYOCARDIAL GLUCOSE PHOSPHORYLATION AND THE DNA MUTATION 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 i n the 3' untranslated region of a protein kinase gene located on chrom osome 19. Impaired glucose metabolism has been suggested as a possible explanation of brain and skeletal muscle involvement in this multisys tem 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 metabo lic rate for glucose (MMRGlu, mu mol.min(-1).g(-1)), K1 (blood-to-tiss ue 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 gen erated from dynamic cardiac positron emission tomography (PET) and F-1 8-fluoro-2-deoxyglucose studies. The expansion of the CTG triplet repe ats was analyzed in patients with the probe cDNA25 after EcoRI digesti on. Nonparametric tests were used to compare quantitative variables be tween 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 K1 and k2 were no t statistically different between control subjects and patients. MMRGl u 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, respectiv ely). Conclusions In myotonic dystrophy, the observed reductions in MM RGlu and phosphorylation are inversely linked to the length of the mut ation. This observation suggests that impaired modulation of a protein kinase involved in myocardial hexokinase activation may give a pathop hysiological schema to relate the molecular defect and the abnormal my ocardial metabolism in myotonic dystrophy.