Increased rates of myofibrillar protein breakdown in muscle-wasting diseases.

The excretion of endogenous creatinine and 3-methylhistidine by subjects with muscle diseases has been measured in order to assess muscle mass and fractional rates of myofibrillar protein degradation. Increases in the rates of myofibrillar protein breakdown were observed in all subjects with Duchenne, Becker, autosomal recessive Duchenne-like, and limb-girdle muscular dystrophy; dystrophia myotonica; myotonia congenita; peroneal muscular atrophy; myasthenia gravis; and central core disease; in some cases of spinal muscular atrophy; but in no cases of facioscapulohumeral muscular dystrophy of dystonia musculorum deformans. All increases in myofibrillar protein breakdown were associated with reductions in muscle proportion below the normal. Muscle-wasting diseases may respond to therapy directed towards an inhibition of muscle protease activity; the efficacy of such therapy can be monitored by the 3-methylhistidine-to-creatinine excretion ratio.