“Introduction: Thymidine kinase 2 (TK2) encodes the mitochondrial matrix protein TK2, a critical component of the mitochondrial nucleotide salvage pathway. TK2 deficiency (TK2d) causes mtDNA depletion and/or multiple deletions which manifest predominantly as mitochondrial myopathy. Three main phenotypes are known: 1) early onset form (median survival: < 2 years); 2) childhood-onset form; 3) late-onset form with a variably slower rate of progression. Nucleoside therapy was demonstrated in mice and humans to determine a significant benefit with a favorable side-effect profile. We report a baby girl with a childhood-onset TK2 deficiency who promptly started nucleoside treatment and showed impressive improvement in 20 months of follow-up.
Case report: Our patient showed a normal psychomotor development with autonomous ambulation at 14 months of age. At 23 months she presented at Urgence Department of our Hospital complaining subacute onset of lower limb weakness in the last month. Blood analyses revealed increased CK (2643 U/L), transaminases and LDH values. She underwent a muscle biopsy that showed ragged red and COX-/SDH+ fibers. Serum FGF21 and GDF15 were both increased. NGS analyses disclosed compound heterozygous variants in TK2 (p.Arg183Gly; p.Thr108Met), segregating in the parents. Three months after admission she started nucleoside treatment under compassionate use. Six months later she showed complete CK, FGF21 and GDF15 normalization. In 18 months of follow-up she also showed impressive motor improvement at HFMSE (Baseline 17/66; Last visit 54/66).
Conclusions: This report further outlines the importance of a prompt TK2 diagnosis in childhood forms, in order to possibly start nucleoside therapy.”