Metrics of progression and prognosis in untreated adults with thymidine kinase 2 deficiency: An observational study.

This historical cohort study evaluated clinical characteristics of progression and prognosis in adults with thymidine kinase 2 deficiency (TK2d). Records were available for 17 untreated adults with TK2d (mean age of onset, 32 years), including longitudinal data from 6 patients (mean follow-up duration, 26.5 months). Pearson's correlation assessed associations between standard motor and respiratory assessments, clinical characteristics, and laboratory values. Longitudinal data were assessed by linear regression mixed models. Respiratory involvement progressed at an annual rate of 8.16% decrement in forced vital capacity (FVC). Most patients under noninvasive ventilation (NIV) remained ambulant (12/14, 86%), reduced FVC was not associated with concomitant decline in 6-minute walk test (6MWT), and 6MWT results were not correlated with FVC. Disease severity, assessed by age at NIV onset, correlated most strongly at diagnosis with: creatinine levels (r = 0.8036; P = 0.0009), followed by FVC (r = 0.7265; P = 0.0033), mtDNA levels in muscle (r = 0.7933; P = 0.0188), and age at disease onset (r = 0.7128; P = 0.0042). This population of adults with TK2d demonstrates rapid deterioration of respiratory muscles, which progresses independently of motor impairment. The results support FVC at diagnosis, mtDNA levels in muscle, and age at disease onset as prognostic indicators. Creatinine levels may also be potentially prognostic, as previously reported in other neuromuscular disorders.