Creatine kinase estimation in pure fetal blood samples for the prenatal diagnosis of duchenne muscular dystrophy

Abstract

This paper compares the results of a survey of plasma creatine kinase (CK) activity measured in fetuses at-risk for Duchenne muscular dystrophy (DMD) with a reliable control series. Only pure fetal blood samples obtained by fetoscopy at between 17-24 weeks gestational age were used. Of the at-risk group 19 male pregnancies, mostly at low risk for DMD, proceeded to term with a normal outcome; there was no significant difference between their fetal plasma CK activities and the control group. Another 21 male pregnancies were terminated. This group included the highest risk mothers and hence was expected to contain a significant proportion of affected fetuses. The fetal plasma CK activity range was overlapping but significantly higher than the control group. No grossly elevated CK value was obtained. We conclude that, on average, DMD fetuses at this gestational age have higher plasma CK activity than controls. The problems of applying this finding to the prenatal diagnosis of DMD are discussed.

Duchenne Muscular Dystrophy Newborn Screening: Evaluation of a New GSP® Neonatal Creatine Kinase-MM Kit in a US and Danish Population

“…Another affected newborn, with a gestational age of 35 weeks and birth weight of 2700 g had a CK-MM concentration of 1100 ng/mL i.e., above the used cutoff values. Previous prenatal studies [22] have showed that some affected fetuses do not have elevation in CK. Since the CK-MM is primarily a marker of skeletal muscle damage and thus an indirect marker of Duchenne, Duchenne affected infants may be born who have not yet sustained enough muscle damage to elevate the CK-MM marker above the cut-off level.…”

Primary Role of Functional Ischemia, Quantitative Evidence for the Two-Hit Mechanism, and Phosphodiesterase-5 Inhibitor Therapy in Mouse Muscular Dystrophy

“…This may be due to a downregulation of the effect of the drug after weeks of treatment, or because of possible variations in the extent of ad lib movements of individual animals that will require further investigation. In this study, we prioritized biological question about the efficacy of tadalafil and started the drug treatment before birth and continued during lactation and weaning until 4 weeks of age, based on the fact that myofiber damage in always upregulated in mdx mice and DMD patients even before birth [53], [54] and that this drug has high transplacental distribution capability and is lactationally secreted [55]. Biologically, our data from experiments in tadalafil treatment supports that histological changes are due to the increased turnover of muscle degeneration and regeneration.…”

Pyruvate kinase in fetal plasma and amniotic fluid unsuccessful for the prenatal diagnosis of Duchenne muscular dystrophy

“…Pure fetal blood samples can now be obtained, facilitating the search for an elevated plasma enzyme activity as a diagnostic aid. With this in mind studies have also been made of creatine kinase [Edwards et al, 1984b], myoglobin [Edwards et al, 1984~1, and carbonic anhydrase I11 [Carter et al, 19821. Mildly elevated plasma levels of creatine lunase and carbonic anhydrase I11 found in high-risk fetuses offer promise for the diagnostic use of these two enzymes but myoglobin was found to be of no value.…”