Thymidine kinase 2 deficiency (TK2d) is a rare mitochondrial myopathy caused by pathogenic variants in the TK2 gene. First described in 2001, its true prevalence has remained poorly defined. Without accurate population estimates, clinical awareness is limited, genetic testing sensitivity goes unoptimized, and the case for including TK2d in newborn screening programs is difficult to make.
When prevalence is undefined, patients remain undiagnosed. For a disease where early intervention can change outcomes, evidence gaps in population data are not just academic. They are clinical.
This poster, presented at the European Human Genetics Conference (ESHG 2026) and funded by UCB, presents a comprehensive genetic birth prevalence estimate for TK2d developed through a combined methodology: systematic extraction of TK2 variants from published literature using Mastermind, ACMG/AMP-based expert classification, and allele frequency analysis using gnomAD v4. The study estimated global genetic birth prevalence at 0.34 to 2.82 per million pregnancies, consistent with prior clinical prevalence data. Marked population-level differences were identified, with the highest prevalence observed in Admixed American populations (2.80 to 13.06 per million pregnancies), African/African American populations (0.36 to 8.27 per million), South Asian populations (0.27 to 5.15 per million), and Finnish populations (3.23 to 4.39 per million).
The result: an evidence-based, population-stratified genetic prevalence estimate that can inform diagnostic testing strategies, healthcare planning, and newborn screening feasibility analysis for TK2d.
