Background Mitochondrial DNA (mtDNA) depletion syndromes (MDS) attribute secondary heterogeneous diseases to defects in the mitochondrial respiratory chain. MDS are due to primary defects in nDNA genes that cause secondary defects in mtDNA. One of these genes is TK2, which codifies timidin-kinase (TK2), a necessary mitochondrial enzyme for the phosphorylation of the pyrimidine nucleosides (thymidine and cytidine), giving rise to deoxythymidine monophosphate (dTMP) and deoxycytidine monophosphate (dCMP). Currently, there is no effective treatment for mitochondrial diseases.

Purpose To analyse deoxynucleotide use in mitochondrial diseases.

Material and methods A boy aged 2 years and 10 months presented with progressive weakness and regression of psychomotor development. After 8 months from the beginning of his symptoms, the patient could not walk or remain standing. An investigation of the TK2 gene identified two mutations. Currently, in Columbia University, a favourable effect in animal models has been achieved with oral administration of dTMP and dCMP 200 mg/kg/day which delays disease progression and doubles mice survival rate. This treatment has already being used in three patients worldwide with positive results.

Application and authorisation for compassionate use of these deoxynucleotides, which the patient cannot synthesise, as substitutive therapy, was sought. Review of the patient’s clinical history from diagnosis to his present situation is reported.

Results After 4 months of treatment, the patient has improved his muscular capacity and head support. His parents confirm evident clinical improvement.

Conclusion In patients with a TK2 mutation, positive results and absence of secondary effects with the resulting benefit in health and quality of life are being obtained with deoxynucleotides. Further prospective well designed studies are needed to quantify the possible benefit of these treatments.

References and/or Acknowledgements Eil y Likallio and Anu Suomalainen^1,2

Research Program Unit, Molecular Neurology, Biomedicum-Helsinki, University of Helsinki

Department of Neurology, Helsinki Central Hospital, Helsinki, Finland

No conflict of interest.