Purine and carnitine metabolism in muscle of patients with Duchenne muscular dystrophy

Abstract

We determined levels of purines, purine metabolites, related enzymes and carnitine in muscle of 8 untreated Duchenne muscular dystrophy (DMD) patients, 12 allopurinol-treated DMD patients and 12 age-matched controls. Muscle of DMD patients was found to be deficient in ATP, ADP, adenylsuccinate, hypoxanthine, guanine and adenylsuccinate synthetase. In allopurinol-treated DMD patients, mean total adenylate level was only three times less than in controls (versus 14 times less in untreated DMD patients). Mean inosine monophosphate (IMP), adenine, adenosine, inosine, xanthine, guanine, guanosine and uric acid levels were higher in allopurinol-treated patients than in controls, while mean adenylsuccinate levels were higher than in untreated patients. Allopurinol also 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 blockage of the IMP → purine pathway and that allopurinol treatment favours restoration of purine levels by this route. Furthermore, our results suggest that the observed deficiencies in cell components unrelated to purine metabolism are long-term secondary effects.