Identifying and circumventing the defect in Duchenne muscular dystrophy: clinical and biochemical restoration after...

Both direct and indirect experimental evidence independently confirms that inadequate muscle purine biosynthesis is the basic lesion in Duchenne muscular dystrophy (DMD), and indicates the presence of a partial defect at adenylosuccinate synthetase. Purine conservation by oral allopurinol gives only limited improvement, but continuous infusion of adenylosuccinate causes an immediate and lasting increase in physical strength, with restoration to normal of the abnormal serum enzyme elevations, creatine/creatinine metabolism, heart rate and ECG. Mass screening of male infants by a blood-spot test is proposed for early detection and treatment of all DMD cases, including the mutant one third with no family history. Prospects of the eventual disappearance of clinical DMD now appear possible.