Levels of adenylate deaminase, adenylate kinase, and creatine kinase in frozen human muscle biopsy specimens relative to type 1/type 2 fiber distribution: evidence for a carrier state of myoadenylate deaminase deficiency.

Myoadenylate deaminase deficiency is believed to reflect a genetic deficiency of skeletal muscle, but its pattern of inheritance has not been established. We examined, histochemically and by quantitative biochemical assay, muscle biopsy specimens from 3 putative carriers of this disorder. Adenylate kinase and creatine kinase were assayed in parallel with adenylate deaminase in order to establish enzyme activity ratios and the variation of each enzyme with fiber-type distribution. Control tissue consisted of 34 biopsy specimens without notable abnormalities from 30 patients, and included 4 specimen pairs with disparate fiber-type contributions. By linear regression analysis, adenylate deaminase level averaged 2.8-fold higher, and adenylate kinase 4.5-fold higher, in type 2 than in type 1 fibers, whereas creatine kinase level did not differ. The slopes of the regression lines resulting from analysis of the four specimen pairs from individual patients agreed well with the overall regression line in each plot. The 3 putative carriers had adenylate deaminase levels 2.5 to 5.7 times lower than the mean control value for their fiber-type distribution, but at least 20 times higher than their enzyme-deficient kinfolk. This finding indicates that a carrier state does exist, and that the deficiency state reflects an autosomal recessive inheritance pattern. Three additional biopsy specimens were excluded from evaluation when preliminary analysis showed elevated adenylate kinase/adenylate deaminase ratios that were outliers at the 1% level. This result suggests a carrier incidence of 10% in the muscle biopsy specimen population, which would markedly bias population estimates if undetected.