Thymidine kinase 2 deficiency (TK2d) is estimated to affect between 0.34 and 2.82 per million pregnancies worldwide, according to a new genetic analysis presented recently at the Muscular Dystrophy Association’s 2026 Clinical and Scientific Conference.
“These findings can inform healthcare planning by identifying at-risk populations and may provide data for evaluating the feasibility of TK2 inclusion in newborn screening programs,” said this study’s authors. “The higher estimated genetic prevalence in some populations emphasizes the importance of clinical awareness and early diagnostic testing.”
TK2d is caused by inherited mutations in the TK2 gene. It follows an autosomal recessive pattern, meaning a child must inherit one altered gene from each parent to develop the condition.
First described in 2001, the true prevalence of TK2d has remained unclear. To better understand how often it occurs, investigators used the Mastermind Genomic Search Engine to identify all reported TK2 single-nucleotide variants and small insertions or deletions from published literature. Variants were reviewed and classified according to American College of Medical Genetics criteria as pathogenic, likely pathogenic, variant of uncertain significance or presumed pathogenic, such as loss-of-function variants.
Read more about causes and risk factors of TK2d
The team then estimated genetic birth prevalence using allele frequency data from the gnomAD v4 database, applying Hardy–Weinberg equilibrium calculations. When limiting the analysis to pathogenic and likely pathogenic variants, the lower-bound global estimate was 0.34 per million pregnancies. When all selected variants were included, the estimate rose to 2.82 per million pregnancies.
Higher estimated genetic prevalence and carrier frequency per million pregnancies were observed in American populations of mixed ancestry (ranging from 2.80 to 13.06), African or African American populations (ranging from 0.36 to 8.27), South Asian populations (ranging from 0.27 to 5.15) and Finnish populations (ranging from 3.23 to 4.39). The most common pathogenic variants worldwide were p.Ala139Thr, p.Arg183Trp, p.Ala139Val, p.His121Asn and p.Thr108Met, although their frequency differed across subgroups.
For patients and families, these findings may influence how quickly doctors consider genetic testing when unexplained muscle weakness appears, especially in higher-risk populations. The data could also help health officials evaluate whether TK2d should be added to newborn screening programs. Earlier diagnosis may open the door to faster supportive care and emerging treatments.
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