In 1962, Wieme et al. 1) o bserved differentr elati ve amounts of isozymes in the human dystrophic muscles fr om in the normal ones. Similar results were obtained in the man by Dreyf us et al. 2) and in the chicken by Kaplan et al. 3). They pointed out that abnormality in dystrophy resembles the patterns in the normal foetal muscle, and suggested that the normal adult isozyme pattern fails to develop in muscular dystrophy. Howeve r, these suggestions have been quest ionable 4) on account of a similar composition of lactic dehydrogenase (LDH) obtained in neurogenic atrophies and even in some normal muscles. So, some studies were made to elucidate what the isozyme abnormality was for muscular dystrophy of Duchenne type.
Clinical features were traced out in relation to age. In a 3 years old boywith preclinical signs, there were neither dysfunctions or atrophies of both the shoulders and lower limbs. In a 5 years old boy with the onset of clinical signs, dysfunctions were recognized but no atrophies at all. In a 9 years old boy with the advanced signs, both dysfunctions and atrophies appeared. The figure of this case looks like that of steroid myopathy caused by glucocorticoid, which is derived from a stronger damage in the white muscle than in the red one 8). In a 15 years old boy, extreme wasting was visible on all muscles. This process leads us to the conclusion that the wasting in Duchenne type is initiated in the white muscles of the shoulder girdles and the lower limbs, in which M4 of LDH is involved, and followed in other muscles, in which H2M2 is involved.
Then, the isozyme patterns in the white muscles and the serums were traced out. LDH, which were caught in the muscles of the preclinical boy, was M4 as an adult type instead of H2M2 as a human foetal type and showed only a slight decrease in activity. The M4 was more decreased in the 5 years old boy and lost finally in the 9 years old boy. There, obvious appearances of the isozyme abnormalities were observed as a result of the M4 loss. In parallel with these findings in the muscles, the isozyme patterns of the serum showed also a gradual decrease in M4 in relation to age. It may be said therefore that the features of the serum reflect that of the muscle.
In a case of the early stage of muscular dystrophy, both the muscles and the serums were rich in M4. This fact indicates scme leakage of M4 frcm the muscles into the serums, namely the impaired membrane. But it seems less likely to be the primarily impaired membrane, but to be the secondarily impaired one for this disease. Was such a impaired membrane to be primary, M4 must be unable to be detected even in the preclinical boy in view of some hereditary factor associated with the membrane since birth.
The gradual decrease in serum enzyme activity in relation to age was found also in FDPaldolase and creatine kinase. Such enzymes as LDH, FDP-aldolase and creatine kinase show all higher activities in a white muscles than in a red muscles, and make the phasic movements specific for the white muscles 5, 7, 8). The features of an adult muscle, described above, are not found in an embryo but appear with time according to developements and differentiations of the muscles 7), contrary to the features of muscular dystrophy. These findings may lead us to suggest that “ escape ” of the adult feature-dedifferentiation of the white muscle and afterwards other tissues (In the latter, it is shown by a result of elevation of the F1P-aldolase activity, in the serum of advanced dystrophy, unable to be found in the white muscles) is the essence of muscular dystrophy. The changes of LDH isozymes constitute only one part of the dedifferentiation.
