Creatine kinase-MM concentration in dried blood spots from newborns and implications for newborn screening for Duchenne muscular dystrophy

Abstract

Introduction/Aims: Creatine kinase-MM (CK-MM) is a marker of skeletal muscle damage. Detection of elevated levels of CK-MM in newborns can enable an early suspicion of the diagnosis of Duchenne muscular dystrophy (DMD) before symptom onset. Our aim was to investigate CK-MM levels in DMD-affected and unaffected newborns using an immunoassay that measures CK-MM concentration in dried blood spots collected for routine newborn screening. Methods: To validate the assay in our laboratory, CK-MM measurements and newborn demographic information were collected for 8584 de-identified specimens and 15 confirmed DMD patients. After analyzing validation data, CK-MM normal ranges were determined based on age of newborn at specimen collection. Subsequently, the assay was used to measure CK-MM concentration in 26 135 newborns as part of a consented pilot study to screen for DMD in New York State. Mean and median levels of CK-MM based on age of collection, in addition to the 2.5th, 50th, 97.5th, and 99.5th percentiles, were recalculated using the validation and screening data sets. Results: Median CK-MM within 1 hour of birth was 109 ng/mL, rose to a high of 499 ng/mL at 25 hours of age, and then declined to 200 ng/mL at 2 days of life. The median continued to decline more slowly and then stabilized at approximately 40 ng/mL at 1 week of life. Discussion: Because of the marked variability and elevated CK-MM levels observed within the first days of life, it is important to set multiple CK-MM age-related cut-offs when screening for DMD in newborns.