National diagnostic gaps for TK2 Deficiency in Italy: insights from the AIM Multicenter Survey

Objective. Thymidine kinase 2 (TK2) deficiency is a rare mitochondrial disease with variable phenotypes and emerging treatments. Prompt diagnosis is essential to optimize patient outcomes and management. To assess the current awareness, diagnostic approaches, and readiness to include TK2 screening in Italian neuromuscular clinical practice.

Methods. A nationwide survey was distributed to AIM-affiliated clinicians. The questionnaire assessed TK2 awareness, diagnostic pathways, gene panel content, and attitudes towards screening in unresolved cases.

Results. while awareness of TK2 deficiency was almost universal, inclusion of TK2 in genetic panels varied: 85% in metabolic myopathy panels, 56% in LGMD panels. Screening for TK2 in genetically unsolved SMA, FSHD, and OPMD phenotypes was inconsistent. 

Conclusions. Although awareness of TK2 deficiency is widespread, diagnostic strategies are inconsistent. Standardizing TK2 inclusion in NGS panels and promoting differential screening are key steps toward earlier diagnosis in the view of future treatment options.