To describe the clinical and genetic characteristics of late onset TK2 patients from Turkey

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. Here, we present the clinical and genetic findings of three patients from two unrelated families with late on set TK2 deficiency.

The mean age of onset was 17 years (ranges 14-24 years). The mean duration of the disease was 10.6 years (range 7 to 14 years). The first symptom was muscle limb weakness in two patients, swallowing difficulties and respiratory insufficiency in one patient. One patient had vomiting and diarrhea episodes. None of our patients had cognitive involvement. All had bilateral ptosis with normal eye movements, nasal speech and tongue weakness. All developed neck weakness and proximal extremity weakness during the course of the disease. Two patients needed PEG due to severe swallowing difficulties at the age of 15 and 29 years. All patients showed evidence of respiratory muscle weakness and needed non-invasive mechanical ventilation. Serum creatine kinase levels were mildly elevated. Muscle biopsy of two patients showed dystrophic changes with classical signs of mitochondrial dysfunction. All carried the homozygous missense (NM_004614, NP_004605) c.323C>T (p.Thr108Met) mutation in the  TK2 gene.