Introduction: Thymidine kinase 2 deficiency (TK2d) is a rare, life-threatening mitochondrial disease caused by autosomal recessive TK2 mutations. Global prevalence is estimated at 1.64 per 1,000,000, but epidemiologic and natural history data remain limited. TK2d manifests as progressive, proximal, bulbar and facial muscle weakness often leading to severe respiratory involvement. This retrospective study describes the disease course, progression, and healthcare resource utilization in a cohort of TK2d patients at Rady Children’s Hospital San Diego (RCHSD).
Methods: De-identified electronic medical records from RCHSD patients with confirmed TK2d were examined for: demographics; age at symptom onset, diagnosis, and death; motor milestone acquisition/loss; ventilatory and feeding support; and healthcare utilization.
Results: Six patients (3 male, 3 female), all Hispanic/Latino, were included; 5 had genetic confirmation, one was assumed based on an affected sibling. Mean age at diagnosis was 16.1 years (range: 7.7-23.7). All were alive at last follow-up; 3 transitioned to adult care, 3 remain under care. Average symptom onset was 3.6 years (range: 1.9-8.8 years), with early symptoms including gait difficulty (n=3), proximal weakness (n=2) and loss of mobility (n=1). All achieved normal early milestones prior to symptom onset.
Before diagnosis, all underwent creatine kinase testing and muscle biopsy. Differential diagnoses included dystrophies and mitochondrial diseases. All became wheelchair users (mean age 7.0 years; range: 4.0-12.2) and ventilator users (mean age 11.1 years; range: 8.7-14.2). Four are ventilator dependent. Five had hospitalizations (mean age at first stay 9.5 years; 0.3 admissions/year). Patients averaged 91.3 outpatient visits annually, common specialties include: Muscle Disease, Neurology, Sleep, and Pulmonology.
Conclusion: This study provides critical insights into the clinical course of TK2d and associated healthcare burden in a pediatric cohort. These descriptive findings contribute to the limited literature, underscoring the need for early diagnosis, proactive patient management, and multidisciplinary care. Study funded by UCB.