533P Long-term follow-up deoxynucleoside therapy for late onset thymidine kinase 2 deficiency patients.

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 which encodes for mitochondrial thymidine kinase, 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 thymidine kinase 2 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 6-minute walk test (6MWT) and 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, 350m after 6 months and 398m after 12 months, 417m after 18 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% 12 months and 56.6 18 months of treatment. Mean HFMS was 34.7 at baseline, 41.7 at 3th month, 47.7 at 6th month and 54 at 12th and 55.3 at 18th month 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 18th month. All patients gained weight, mean BMI was 15.5 at the baseline and 21 after 12 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. [ABSTRACT FROM AUTHOR]