Serum Enzyme Variations and Histological Abnormalities in the Carrier State in Duchenne Dystrophy.

It is generally agreed that the Duchenne form of muscular dystrophy is transmitted as a sex-linked recessive trait with a high mutation rate. The female may be a carrier, but the clinical manifestations of the disease will be limited to males. The occasional expression in the female has been explained by either autosomal recessive inheritance (Dubowitz, 1960) or the mating of a carrier female with a male from whom the X-chromosome has been eliminated during the process of fertilization, giving rise to an X-O female (Walton, 1956). More recently Lyon's hypothesis of X-chromosome mosaicism has been suggested as an explanation for the occurrence of minor clinical features of the disease in female carriers (Emery, 1963; Pearson, Fowler, and Wright, 1963). Lyon (1961) proposed that in all female mammalian somatic cells one Xchromosome became inactive early in embryonic life, that in any given cell this might be the paternal or maternal X-chromosome, and that the descendents of this cell would have the same genetic characters. If this hypothesis be true, then in the female carrier of Duchenne dystrophy, any individual muscle fibre might be normal if its characteristics were determined by the normal paternal X-chromosome or dystrophic if determined by the abnormal maternal X-chromosome. Thus, the carrier would have two populations of muscle fibres, normal and dystrophic, and whether or not there were clinical manifestations of the disease would depend on the proportion of dystrophic fibres. It is known that there is markedly increased activity of a number of enzymes in the serum of patients with Duchenne dystrophy, particularly creatine phosphokinase. Supposedly, in this condition, the muscle membrane is altered, allowing the intracellular enzymes to leak into the serum (Thomson, 1962). The demonstration of elevated serum enzyme levels in the predystrophic stage of affected males