A Retrospective Study of Subjects With Thymidine Kinase 2 Deficiency

Study Overview
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Brief Summary
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This is a multicenter, multinational, retrospective chart-review study to evaluate survival in patients with Thymidine Kinase 2 deficiency (TK2d).

Detailed Description
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This is a retrospective, chart-review study. The primary goal is to use data on survival and other related information to support a comprehensive evaluation of patients with Thymidine Kinase 2 deficiency (TK2d) who have not been treated with pyrimidine nucleos(t)ides including deoxycytidine monophosphate/deoxythymidine monophosphase (dCMP/dTMP), and deoxycytidine/deoxythymidine (dC/dT), and/or MT1621(dC/dT), and those that have received one or more of these treatments. The secondary goals of this study will focus on describing the participant's clinical course and treatment experience.

Official Title
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A Retrospective Study of Subjects With Thymidine Kinase 2 Deficiency Treated With the Combination of Pyrimidine Nucleos(t)Ides as Well as Untreated Subjects to Collect Vital Status Data and Supporting Information

Conditions
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Thymidine Kinase 2 Deficiency

Intervention / Treatment
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* Other: Observational retrospective data


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent by the subject or parent(s)/LAR and/or assent by the subject (when applicable), unless the associated IRB or EC provides an appropriate consent waiver that allows review of medical records for this study. Confirmed genetic mutations in the TK2 gene. Availability of medical records or information pertaining to vital status at a minimum. Exclusion Criteria: Not applicable as this is a non-interventional study.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Treated and untreated subjects with TK2 deficiency<br>Two TK2 deficiency groups. (1) Subjects treated with chemical-grade dCMP/dTMP, dC/dT, and/or MT1621 outside of a Modis sponsored study. (2) Subjects not treated with chemical-grade dCMP/dTMP, dC/dT, and/or MT1621 outside of a Modis sponsored study. | Other: Observational retrospective data<br>* Non-intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who have died. | Participant date of death or date last known alive. | Start of observation period (first medical record available on site), to last medical record available on site or end of observation period on 12-Jan-2022, whichever comes first. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in development motor milestones. | Modified motor milestones as defined by World Health Organization include: Ability to Hold head upright, unassisted; Ability to roll from supine to sides; Ability to sit upright, unassisted; Ability to sit upright, slightly assisted; Ability to raise self and stand; Ability to stand, unassisted; Ability to stand, assisted; Ability to walk, unassisted; Ability to walk, assisted; Ability to climb stairs, unassisted; Ability to climb stairs, assisted; Ability to jump; Ability to hop; Ability to run | Start of observation period (first medical record available on site), to last medical record available on site or end of observation period on 12-Jan-2022, whichever comes first. | 
| Change from baseline in feeding support. | Feeding support includes gastrostomy tube or nasogastric tube. | Start of observation period (first medical record available on site), to last medical record available on site or end of observation period on 12-Jan-2022, whichever comes first. | 
| Change from baseline in respiratory support. | Respiratory support includes non-invasive ventilation (e.g. bi-level positive airway pressure [Bi-PAP]) and mechanical ventilation. | Start of observation period (first medical record available on site), to last medical record available on site or end of observation period on 12-Jan-2022, whichever comes first. | 
| Clinical Global Impression of Improvement (CGI-I). | The CGI-I is a 7-point Likert scale would have been conducted by a physician or trained rater at a clinic visit to establish overall clinical change. | Start of observation period (first medical record available on site), to last medical record available on site or end of observation period on 12-Jan-2022, whichever comes first. | 
| Number of participants with treatment-emergent adverse events (AEs) or serious adverse events (SAEs) that cause a decrease in dose or a stop in dosing (temporary or permanent). | An AE is any untoward medical occurrence in a participant that was receiving treatment without regard to causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, congenital anomaly. SAEs were AEs excluding non-serious AEs. | Start of observation period (first medical record available on site), to last medical record available on site or end of observation period on 12-Jan-2022, whichever comes first. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TK2D, mitochondrial disorder, mitochondrial disease, mitochondria, primary mitochondrial myopathy, mitochondrial depletion syndrome, muscle weakness, muscle atrophy, loss of mobility