Late-onset thymidine kinase 2 deficiency (TK2d) steadily worsens over time, affecting both muscle strength and breathing even in adults who develop symptoms later in life, according to a study published recently in the Journal of Inherited Metabolic Disease.
Researchers followed 11 untreated adults for two years and found measurable declines in physical function and lung capacity, helping clarify what patients can expect and how doctors may monitor the disease.
Unlike childhood forms of TK2d, late-onset disease can begin after age 12 and may appear as exercise intolerance, eye muscle problems or progressive muscle weakness. In this study, the average age of symptom onset was 27.2 years and patients had lived with the disease for more than 20 years on average.
Most patients had progressive muscle weakness, while others mainly experienced exercise intolerance or eye movement problems. Many also had breathing involvement. About 72% required noninvasive mechanical ventilation, often beginning around age 50. Lung function steadily declined, with forced vital capacity dropping by 9.11% over 24 months and much more in those with progressive muscle disease.
Read more about the prognosis of TK2d
“These findings underscore the urgent need to evaluate the potential benefits of nucleoside therapy in this age group,” said the study’s authors.
Muscle testing showed meaningful changes patients might notice in daily life. Over two years, walking and running ability worsened, with patients taking about six seconds longer to complete a 100-meter run. Those with progressive muscle weakness declined the most. In contrast, the six-minute walk test stayed relatively stable, suggesting some tests are better than others for tracking change.
Blood tests and imaging also helped explain what was happening inside the muscles. All patients had elevated levels of GDF15, a marker linked to worse muscle and breathing function. Muscle MRI showed fat replacing muscle tissue in specific areas, which closely matched poorer movement. Muscle biopsies confirmed damage to mitochondria, the cell’s energy producers.
For patients, these findings offer clearer expectations and practical benefits. The study identifies tests that reliably show change over time, which can help doctors monitor disease progression and plan care. Just as important, the results provide a roadmap for future clinical trials, raising hope that emerging treatments could be tested more effectively in adults with this rare condition.
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