Abstract
Thymidine kinase 2 (TK2) deficiency is an ultrarare mitochondrial depletion and deletion syndrome characterized by mutations in the nuclear TK2 gene responsible for encoding the mitochondrial thymidine kinase 2 enzyme. TK2's role is to phosphorylate the nucleosides deoxycytidine (dC) and deoxythymidine (dT) required for mitochondrial DNA (mtDNA) replication; therefore, deficient TK2 enzymes result in dysfunctional replication of mtDNA. TK2 deficiency presents in children as progressive muscle weakness, respiratory difficulty, and mtDNA depletion. Fewer than 120 patients have been described in medical literature, and there are currently no FDA-approved treatments for TK2 deficiency. Provision of exogenous deoxynucleosides (dC/dT) allow for replication of mtDNA via cytosolic enzymes thymidine kinase 1 (TK1) and deoxycytidine kinase (dCK), as well as any residual TK2 activity. Here we describe a 26-year-old female with childhood-onset TK2 deficiency characterized by progressive myopathy, fatigue, weight loss, atrophy, bone fractures, dysphagia, neuropathy, and respiratory failure. With initiation of deoxynucleoside therapy and multiple therapy modalities (physical, occupational, and speech), her rate of decline slowed and she has shown steady improvement.
