%0 Case Reports
%T Remarkable clinical improvement with oral nucleoside treatment in a patient with adult-onset TK2 deficiency: A case report.
%A Bermejo-Guerrero L
%A Hernández-Voth A
%A Serrano-Lorenzo P
%A Blázquez A
%A Martin-Jimenez P
%A Martin MA
%A Domínguez-González C
%J Mitochondrion
%V 76
%N 0
%D 2024 May 9
%M 38599303
%F 4.534
%R 10.1016/j.mito.2024.101879
%X <B>OBJECTIVE: </B>Thymidine kinase 2 deficiency (TK2d) is a rare autosomal recessive mitochondrial disorder. It manifests as a continuous clinical spectrum, from fatal infantile mitochondrial DNA depletion syndromes to adult-onset mitochondrial myopathies characterized by ophthalmoplegia-plus phenotypes with early respiratory involvement. Treatment with pyrimidine nucleosides has recently shown striking effects on survival and motor outcomes in the more severe infantile-onset clinical forms. We present the response to treatment in a patient with adult-onset TK2d.<BR><B>METHODS: </B>An adult with ptosis, ophthalmoplegia, facial, neck, and proximal muscle weakness, non-invasive nocturnal mechanical ventilation, and dysphagia due to biallelic pathogenic variants in TK2 received treatment with 260 mg/kg/day of deoxycytidine (dC) and deoxythymidine (dT) under a Compassionate Use Program. Prospective motor and respiratory assessments are presented.<BR><B>RESULTS: </B>After 27 months of follow-up, the North Star Ambulatory Assessment improved by 11 points, he walked 195 m more in the 6 Minute-Walking-Test, ran 10 s faster in the 100-meter time velocity test, and the Forced Vital Capacity stabilized. Growth Differentiation Factor-15 (GDF15) levels, a biomarker of respiratory chain dysfunction, normalized. The only reported side effect was dose-dependent diarrhea.<BR><B>CONCLUSIONS: </B>Treatment with dC and dT can significantly improve motor performance and stabilize respiratory function safely in patients with adult-onset TK2d.