PURINE AND CARNITINE METABOLISM IN MUSCLE OF PATIENTS WITH DUCHENNE MUSCULAR-DYSTROPHY

We determined levels of purines, purine metabolites, related enzymes a nd carnitine in muscle of 8 untreated Duchenne muscular dystrophy (DMD ) patients, 12 allopurinol-treated DMD patients and 12 age-matched con trols. Muscle of DMD patients was found to be deficient in ATP, ADP, a denylsuccinate, hypoxanthine, guanine and adenylsuccinate synthetase. In allopurinol-treated DMD patients, mean total adenylate level was on ly three times less than in controls (versus 14 times less in untreate d DMD patients). Mean inosine monophosphate (IMP), adenine, adenosine, inosine, xanthine, guanine, guanosine and uric acid levels were highe r in allopurinol-treated patients than in controls, while mean adenyls uccinate levels were higher than in untreated patients. Allopurinol al so restored acylcarnitine levels to normal and significantly increased free carnitine levels. These findings strongly support the hypothesis that Duchenne muscular dystrophy involves alterations leading to bloc kage of the IMP --> purine pathway and that allopurinol treatment favo urs restoration of purine levels by this route. Furthermore, our resul ts suggest that the observed deficiencies in cell components unrelated to purine metabolism are long-term secondary effects.