More Than a Myopathy: The Lived Experience of TK2d

Thymidine kinase 2 deficiency (TK2d) is defined clinically by progressive myopathy, but its impacts on patients extend well beyond muscle weakness. A 2026 international survey published in Therapeutic Advances in Rare Disease found that breathing, mobility, eating, social life, and independence erode over time.

The Assessment of TK2d Patient Perspectives study shifts the lens from clinical manifestations to daily life. Investigators paired quantitative survey data with patients' and caregivers' own accounts of living with progressive functional loss.

A Broader View of Disease Burden
The cross-sectional study enrolled 32 patients from 12 countries and territories across North America, Europe, South America, and Asia. Twenty-four responded directly, and caregiver proxies answered for the remaining 8. All 3 commonly described age-of-onset groups were represented: 12 patients with onset at ≤2 years, 10 at >2 to ≤12 years, and 10 at >12 years. Notably, 8 patients had received pyrimidine nucleos(t)ide therapy through expanded access or compassionate-use programs, but the survey did not compare experiences before and after treatment.

All patients reported muscular or myopathic symptoms. Fatigue was most common, affecting 29 of 32 patients, followed by upper-body muscle weakness in 27 and lower-body weakness in 25. Other symptoms included neurologic symptoms (29/32), psychological symptoms (25/32), gastrointestinal symptoms (17/32), and musculoskeletal symptoms (11/32).

Function took the hardest hit. Twenty-six patients reported impairment in basic activities of daily living, including walking, eating, swallowing, and breathing difficulties. Every patient with impaired walking attributed it to muscle weakness, and weakness was also behind most cases of swallowing difficulty.

Earlier Onset Tracked with Greater Functional Impact
Patients whose symptoms began earliest appeared to carry the heaviest burden. Participants rated how much specific difficulties affected their health-related quality of life on a 0-4 scale. Those with onset at ≤2 years gave a median score of 4 for both breathing and walking difficulties.

Device use followed a similar pattern. Overall, 22 of 32 patients required equipment for breathing, walking, or eating. 20 used respiratory support, 10 used walking aids or wheelchairs, and 8 required nasogastric or gastrostomy feeding. Support needs were substantial across the cohort, only 3 patients could perform normal activities without assistance or modification, while 13 needed full-time support.

The study also illustrates how progressive physical impairment can reshape participation in work, education, and social life. TK2d negatively affected social and leisure activities in 27 of 32 patients, mood in 25, and employment or education in 23. Qualitative responses described fatigue-driven activity planning, growing dependence on caregivers, anxiety about disease progression, social isolation, and fear related to reliance on medical equipment.

Adapting Daily Life
Patients described breathing support, feeding adaptations, and mobility devices as necessary but restrictive. Respiratory equipment could interfere with sleep, self-care, and leaving the home. Walking impairment limited household tasks, employment, and social participation, while fear of falls further eroded independence. Eating and swallowing difficulties turned meals into carefully managed activities involving modified foods, supervision, or feeding devices, sometimes reducing participation in social events centered around food.

In terms of healthcare utilization, 19 patients spent at least a day in the hospital during the preceding year, while 20 had at least 10 healthcare appointments. Over half of patients aged 18 years or older spent at least 5 hours per month coordinating their care.

Clinical Implications for TK2D Care
The findings come with caveats. Despite the sample size being high in the context of an ultra-rare disease, the sample size prevents inferential comparisons between onset groups. Recruitment relied on opportunity sampling, all clinical information was self-reported, and patients with the most rapidly progressive early-onset disease were likely underrepresented.

Nevertheless, the findings reinforce that TK2d management involves more than monitoring muscle weakness. Functional decline, respiratory and nutritional support, psychosocial health, caregiver dependence, and care coordination are intertwined parts of the disease experience, and keeping all of them in view may help clinicians spot shifting support needs as the disease advances.

Reference:
Karaa A, Hareendran A, Waller K, et al. Patients’ lived experience of thymidine kinase 2 deficiency: the online survey-based assessment of TK2d patient perspectives study. Ther Adv Rare Dis. 2026;7:1-17. doi:10.1177/26330040261469197.