CK-MM screening using neonatal dried blood spots may be inadequate at detecting all dystrophin mutation carriers

We read with interest the article by Qian et al. on a closed, prospective cohort study of the clinical and analytical validity of screening for the creatine kinase MM isoenzyme (CK-MM) for the detection of newborns at risk for Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) using dried blood spots (DBS) (1). Of 42,862 male newborns, 214 had elevated CK-MM levels (1). Of 184 patients who returned for further testing, total serum CK was elevated in only 10 patients, 8 of whom tested positive for DMD via next-generation sequencing (NGS) (1). Of 30 patients who did not attend the follow-up examination, DMD was genetically confirmed in three of them (1). A cutoff value of >700 ng/mL CK-MM was found to be suitable for identifying newborns with DMD/BMD (1). The study is interesting but requires further discussion.

First, it is unclear how DMD could be distinguished from BMD based on blood tests or genetic test results (1). There are no hotspot mutations that point to either of the two conditions. The best way to distinguish DMD from BMD is through a muscle biopsy. While dystrophin is completely absent in immunohistology in DMD patients, reduced or residual dystrophin is detectable in muscle biopsies from BMD patients. Were those who tested positive for a dystrophin mutation also subjected to a muscle biopsy?

The second point is that there was no discussion regarding the limitations of the DBS used for CK-MM measurement, specifically concerning the fact that DMD/BMD does not necessarily manifest phenotypically in skeletal muscle at the onset of the disease in all patients with a dystrophin mutation, but rather in the myocardium with dilated cardiomyopathy or arrhythmias (2). In this case, CK-MM levels may appear normal, and a patient with DMD/BMD genes could have been overlooked. Were patients who tested positive for CK-MM also tested for CK-MB?

The third point concerns the discrepancy between the statement in the “Methods” section, which states that blood for the DBS was collected within three days of birth, and the statement in the “Results” section, which states that only 49% of the newborns were three days old at the time of the DBS, while 42% were four days old, 3.6% were five days old, 1.6% were six days old, and 0.9% were seven days old (1). This discrepancy should be clarified.

The fourth point is that some patients had elevated CK-MM levels but did not have DMD/BMD or any other myopathy (1). What was the reason for the elevated CK-MM levels in these patients? How can an elevated CK-MM level be explained in the absence of neuromuscular disease? Were there signs of birth trauma? Did any of these babies experience seizures or rhabdomyolysis within the first three days of life?

The fifth point is that no explanation was provided as to why the CK-MM level was elevated in the DBS but not in the serum CK measurement. What was the reason for the temporarily elevated CK-MM level at birth?

The sixth point is that female newborns were excluded from the analysis (1). Although female carriers generally do not exhibit the full clinical picture of DMD/BMD as men do, they may present clinically with a milder phenotype, though in some patients with severe dilated cardiomyopathy (3). Therefore, it is recommended that not only male newborns but also female newborns, whenever possible, be screened for CK-MM.

Overall, newborn screening using DBS is beneficial, but it should also include female newborns. It is also recommended to measure total CK, as this allows for the identification not only of muscle disorders but also of patients with brain and heart conditions.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was a standard submission to the journal. The article did not undergo external peer review.

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0450/coif). The authors have no conflicts of interest to declare.

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References

1. Qian G, Yang R, Huang X, et al. Neonatal screening for Duchenne muscular dystrophy in eastern China: a closed prospective study. Transl Pediatr 2026;15:72. [Crossref] [PubMed]
2. Del Rio-Pertuz G, Morataya C, Parmar K, et al. Dilated cardiomyopathy as the initial presentation of Becker muscular dystrophy: a systematic review of published cases. Orphanet J Rare Dis 2022;17:194. [Crossref] [PubMed]
3. Lim KRQ, Sheri N, Nguyen Q, et al. Cardiac Involvement in Dystrophin-Deficient Females: Current Understanding and Implications for the Treatment of Dystrophinopathies. Genes (Basel) 2020;11:765. [Crossref] [PubMed]