Studies on the carrier state in X-linked recessive (Duchenne) muscular dystrophy

Observations in 12 normal women and 12 female carriers of X-linked recessive Duchenne muscular dystrophy (DMD), of whom 4 had symptoms and 8 had none, were compared between all 4 groups and with those in 2 DMD boys, one active and one crippled. Carrier symptoms were readily ascertained by systematic examination. Measurement of both lower legs in all 24 women showed neither calf enlargement nor asymmetry in carriers beyond normal variation. Two DMD carrier daughters were noted of the same DMD carrier mother but by different fathers. Whole body counting showed the biological half-life of previously administered 86Rb to be much reduced in DMD, but no differences were found between normal women and any group of carriers. The test is thus valueless for carrier detection, and reasons are given why it should be so. Simultaneous measurement of total body K+, with subsequent determination by isotope dilution of total body water as 3H2O space and extracellular water as NH4 82Br space, showed increased intracellular water and reduced intracellular K+ concentration in all carriers, as if due to osmotic causes, with actual loss of muscle mass and slight diminution of serum K+ in the 4 symptomatic carriers only. Because of diurnal and other variations, the means and standard deviations for six serum enzymes from six fortnightly assays in all subjects were used to measure precise individual status. Their coefficients of variation were abnormal only in symptomatic carriers and ambulant DMD, easily overtexed by even accustomed exertion. This is shown to support previous propositions on the pathogenesis of DMD and the escape of muscle cell content into the circulation.