Related Experiment Video
Updated: Jun 29, 2025
Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
Clinical and Genetic Analysis of Patients With TK2 Deficiency
Francisco Ceballos1, Pablo Serrano-Lorenzo1, Laura Bermejo-Guerrero1
1From the Spanish Network for Biomedical Research in Rare Diseases (CIBERER) (F.C., P.S.-L., A.B., Jorge Amigo, P.M., C.A., E.G.-A., N.M., T.J., A.N., J. Arenas, A.C., R.M., M.A.M., C.D.-G.); Mitochondrial and Neuromuscular Research Group '12 de Octubre' (P.S.-L., A.B., J. Arenas, M.A.M., C.D.-G.), Hospital Research Institute (imas12); Neurology Department (L.B.-G.), Neuromuscular Disorders Unit, Hospital 12 de Octubre; Genetics Department (J.F.Q.-E., M.A.M.), Hospital Universitario 12 de Octubre, Madrid; Fundación Pública Galega de Medicina Xenómica (FPGMX) (J. Amigo, A.C.); Genetic's Group (J. Amigo, A.C.), Santiago de Compostela Research Institute (IDIS); Medicine Xenómica's Group (J. Amigo, A.C.), Research Center for Molecular Medicine and Chronic Diseases (CIMUS), Santiago de Compostela University (USC); Department of Genetics and Genomics (P.M., C.A.), Instituto de Investigación Sanitaria-Fundación Jiménez Díaz University Hospital; Bioinformatics Unit (P.M.), Health Research Institute-Fundación Jiménez Díaz University Hospital, Universidad Autónoma de Madrid (IIS-FJD, UAM), Madrid; Department of Clinical and Molecular Genetics (E.G.-A.), Valld'Hebron University Hospital; Research Group on Neuromuscular and Mitochondrial Disorders (E.G.-A., R.M.), Vall d'Hebron Research Institut (VHIR), Universitat Autónoma de Barcelona; Neuromuscular Unit (N.M.), Department of Neurology, Hospital Universitari I Politècnic La Fe, Neuromuscular and Ataxias Research Group, Instituto de Investigación Sanitaria La Fe; Department of Genetics (T.J.), Hospital Universitari I Politècnic la Fe de Valencia; Neuromuscular Unit (A.N.), Neurology Department, Sant Joan de Déu Research Institute, Sant Joan de Déu Hospital, Barcelona; Neurology Department (B.G.-R., C.P.), Neuromuscular Disorders Unit, Instituto de Biomedicina de Sevilla, Hospital U. Virgen del Rocío; and Spanish Network for Biomedical Research in Neurodegenerative Diseases (CIBERNED) (C.P.), Madrid, Spain.
Thymidine kinase 2 deficiency (TK2d) is often late-onset, particularly in Spain due to specific variants and consanguinity. Increased awareness is crucial for early intervention in this mitochondrial DNA maintenance disorder.
Area of Science:
- Genetics
- Mitochondrial Biology
- Neurology
Background:
- Thymidine kinase 2 deficiency (TK2d) is a rare, autosomal recessive disorder impacting mitochondrial DNA maintenance.
- TK2d is linked to mitochondrial DNA depletion or multiple deletions, causing myopathy.
- While often fatal in children, milder adolescent/adult-onset forms exist, potentially underdiagnosed.
Purpose of the Study:
- To characterize the clinical phenotype of TK2d in a Spanish patient cohort.
- To investigate the genetic basis and prevalence of specific TK2 variants in Spain.
- To highlight the frequency of late-onset TK2d.
Main Methods:
- Retrospective analysis of 53 patients with biallelic TK2 pathogenic variants from 7 Spanish centers.
- Investigation of allele frequencies, common ancestor haplotypes, and variant coalescence using Runs of Homozygosity.
- Clinical data compilation focusing on symptom onset and disease progression.
Main Results:
- 60% of patients (32/53) presented symptoms after age 12 (late-onset).
- Two specific TK2 variants (p.Lys202del, p.Thr108Met) are significantly more prevalent in Spain, likely due to founder effects and consanguinity.
- Late-onset cases frequently carried the p.Lys202del variant (46.9%).
Conclusions:
- Increased prevalence of specific TK2 variants and consanguinity contribute to higher TK2d frequency in Spain.
- The high proportion of late-onset cases suggests potential underdiagnosis in other populations.
- Raising awareness of TK2d is vital for timely diagnosis and intervention, improving patient outcomes.
