To describe the baseline characteristics, treatment and safety outcomes of the patients with late onset TK2 deficiency treated with deoxynucleoside monophosphates and deoxynucleoside in our clinic.

Recessive mutations in the TK2  cause a rare mitochondrial depletion/multiple deletions syndrome. Late-onset TK2 deficiency is very rare and usually manifests as myopathy. There was only one observational multicenter study describing the results of deoxynucleoside therapy previously. Deoxynucleoside monophosphate and deoxynucleoside therapies have not been approved yet for the treatment of TK2 deficiency.

We administered deoxynucleoside monophosphates and deoxynucleoside to three late onset TK2-deficient patients under a compassionate use approved by FDA and Ministry of Health of Turkey. We obtained signed informed consent for the treatment from all patients. All patients underwent motor assessments using 6MW, Hammersmith Functional Motor Scale (HFMS). Routine laboratory test, forced vital capacity (sitting and upright), FSS and BMI were also recorded.

The mean age of onset was 17 years (ranges 14-24 years). The distance walked improved in all, mean baseline 6MWT distances was 153m, mean 6MWT distance was 273m after 3 months of treatment, 350m after 6 months and 398 m after 12 months of treatment. Mean FVC 1 year prior to the treatment was 41%, 37% at baseline, 44% after 3 months, 50% after 6 months and 55%. Mean HFMS was 34.7 at baseline, 41.7 at 3th month, 47.7 at 6^th month and 54 at 12^th of treatment. Mean FSS score was reduced by 10 points (from a baseline of 57.3) after 6 months of treatment and was unchanged at 12^th month. All patients gained weight, mean BMI was 15.5 at the baseline and 19 after 6 months of treatment. No treatment related serious adverse event was observed.

Our data indicates favorable and sustained clinical efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies for late onset TK2 deficiency.