Division of Genetics, Wadsworth Center, New York State Department of Health, David Axelrod Institute, Albany, New York, USA.
Muscle Nerve. 2022 Jun;65(6):652-658. doi: 10.1002/mus.27533. Epub 2022 Apr 6.
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.
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.
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.
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.
简介/目的：肌酸激酶-MM（CK-MM）是骨骼肌损伤的标志物。在症状出现前，检测新生儿 CK-MM 水平升高有助于早期怀疑杜氏肌营养不良症（DMD）的诊断。我们的目的是使用测量常规新生儿筛查采集的干血斑中 CK-MM 浓度的免疫分析法，检测 DMD 患儿和非 DMD 新生儿的 CK-MM 水平。
为了在我们的实验室验证该检测方法，收集了 8584 份无身份信息的标本和 15 例确诊的 DMD 患者的 CK-MM 测量值和新生儿人口统计学信息。在分析验证数据后，根据标本采集时新生儿的年龄确定 CK-MM 正常范围。随后，该检测方法用于测量 26135 名新生儿的 CK-MM 浓度，作为在纽约州进行 DMD 筛查的同意试点研究的一部分。根据采集年龄，重新计算了 CK-MM 的均值和中位数水平，以及第 2.5、50、97.5 和 99.5 百分位数，使用验证和筛查数据集。
出生后 1 小时内的 CK-MM 中位数为 109ng/mL，在 25 小时时升高至 499ng/mL，然后在 2 天龄时下降至 200ng/mL。中位数继续缓慢下降，然后在 1 周龄时稳定在约 40ng/mL。
由于在生命的最初几天内观察到明显的变异性和升高的 CK-MM 水平，因此在对新生儿进行 DMD 筛查时，设置多个与年龄相关的 CK-MM 截止值非常重要。
