R. J. Edwards

The diagnostic value of plasma myoglobin levels in the adult and fetus at-risk for Duchenne muscular dystrophy.

In boys with Duchenne muscular dystrophy (DMD) plasma myoglobin levels remained approximately constant with age while creatine kinase (CK) activity progressively decreased. For carrier detection, plasma myoglobin level was found to be less reliable than CK activity. The myoglobin level was raised only in some of those subjects who also showed a raised CK activity and was normal in those with a normal CK activity. The myoglobin level in fetal muscle at 18-22 weeks gestational age was found to be low compared with adult skeletal muscle levels and, consequently, the myoglobin level in fetal plasma and in amniotic fluid was found to be negligible. It is concluded that measurement of myoglobin offers no advantage over CK for the investigation of any aspect of DMD.

Development of carboxypeptidase K (creatine kinase conversion factor) in man

The developmental appearance of carboxypeptidase K in human plasma was determined by quantifying the creatine kinase (CK) isoforms present and by measuring the conversion of tetrathionate-blocked CK in vitro. Analysis of plasmas from second and third trimester fetuses, newborns and adults showed that isoforms were absent from second trimester fetuses, were present in similar amounts in third trimester fetuses and newborns, and had increased to about twice this amount in adults. Carboxypeptidase K activity was correspondingly absent from second trimester fetuses but present in the other three groups in statistically indistinguishable amounts. Carboxypeptidase N was present in all groups although activity was low in second trimester fetuses. Addition of cobalt ions activated both carboxypeptidases K and N in all samples and unmasked carboxypeptidase K in second trimester samples.

Fetal Plasma Carbonic Anhydrase III and Creatine Kinase in Duchenne Dystrophy

Raised levels of creatine kinase (CK) and carbonic anhydrase 111 (CA 111) have been found in the plasma of patients with Duchenne muscular dystrophy (DMD) and there is good correlation between them. CA 111 is also virtually specific to skeletal muscle where it is induced quite early in gestation. These factors suggest the potential usefulness of measuring CA I11 and CK in fetal plasma for prenatal diagnosis of DMD. This was investigated as follows. About 80 individual fetal plasma samples were obtained by fetoscopy from pregnancies not at risk for muscle disorders. Sampling was performed at 18-21 weeks gestation. Particular care was taken in all sample collection and handling procedures to ensure pure fetal blood samples were obtained. Radioimmunoassay of CA I11 and spectrophotometric assay of CK enabled control distributions to be calculated. Upper normal limits were fixed at the 95th percentile for both CK and CA I11 (e.g., for CA 111 see FIG. 1). Eleven at risk fetuses were investigated for CA 111. These were divided into low and high risk groups. All three of the low risk fetuses gave CA 111 values below the 95th percentile and normal babies were born at term. All of the high risk fetuses were terminated. From the combined carrier risk of the mothers, three affected fetuses were predicted in this group. In fact two fetuses had plasma CA I11 levels above the 95th percentile and a third had a level on the 95th percentile. These findings were corroborated by concomitant elevations in CK levels.