Sources of error in the biochemical diagnosis of muscular dystrophy.

Muscular weakness due to classical disease is readily diagnosed; when symptoms are vague, signs equivocal, and the history confused much difficulty may arise. Walton (1956) has reviewed the use in diagnosis of examination of the cerebrospinal fluid, muscle biopsy histology, and electromyography. More recently, assay of the serum enzymes aldolase, glutamic-oxalacetic and glutamic-pyruvic transaminases has proved valuable in distinguishing neurogenic muscular weakness from that due to intrinsic muscle disease. Serum enzyme activities are normal in patients with neurogenic weakness, but are raised, sometimes grossly, in those with muscular dystrophy (Schapira, Dreyfus, and Schapira, 1953; Sibley and Fleisher, 1954; Jacob and Neuhaus, 1954; Dreyfus and Schapira, 1955; Beckmann, 1956; Aronson and Volk, 1956; Siekert and Fleisher, 1956; Evans and Baker, 1957; White and Hess, 1957; Salvi, Ambanelli, Rosati, Carreras, and Mironi, 1959; White, 1959; Kaeser, 1959; Aronson, 1960). These elevations seem due to cellular efflux (Thomson, Leyburn, and Walton, 1960) and are greatest by far in the Duchenne type of dystrophy. The highest values occur in early childhood, diminish as the disease progresses, and are least raised terminally (Schapira, Demos, Schapira, and Dreyfus, 1957; Aronson and Volk, 1957a; Pearson, 1957; Rowland and Ross, 1958; Murphy and Cherniak, 1958; Gentili, 1959; Breton, Gaudier, Traisnel, and Ponte, 1959; Thompson and Vignos, 1959; Kaeser, 1960; Thomson et al., 1960). These diminutions accompany the disappearance of skeletal muscle. Thus in the Duchenne type of dystrophy there is a linear relationship between serum aldolase activity and functional muscle mass (Thompson and Vignos, 1959) or age of the patient (Thomson et al., 1960) in accord with an early onset (Pearson, 1961a) and a constant, rapid evolution (Walton and Nattrass, 1954). Similar, less striking relationships occur (Thomson et al., 1960) in the