Limb-girdle muscular dystrophies (LGMDs) are a group of muscular diseases characterized by predominant proximal muscle weakness. Phenotypically, LGMD subtypes are highly variable in terms of age of onset, speed of disease progression, and overall severity; at a histopathological level, their common feature is progressive muscle degeneration with connective tissue substitution, CK elevated and degenerative changes found in Muscle MRI, although they do not share a common pathological mechanism. The incidence for all forms is 1:100,000, and LGMD are divided into two major subgroups: autosomal dominant forms (LGMD type D) and autosomal recessive (LGMD type R). We report a novel Slovakian patient with all these clinical features and entertain a hypothesis regarding the “locking” symptoms that LGMD1F/D2 patients experience.
- Open Access
- Case Report
The Interplay of Infection, Pain, and Locking Syndrome in LGMD-TNPO3 Related Evidence from a Sporadic Slovakian Patient
- Corrado Angelini 1,
- Alicia A. Rodríguez 2
Author Information
Received: 26 Jun 2025 | Revised: 27 Aug 2025 | Accepted: 10 Sep 2025 | Published: 03 Dec 2025
Abstract
Keywords
References
- 1.
Aguti, S.; Gallus, G.N.; Bianchi, S.; et al. Novel biomarkers for limb girdle muscular dystrophy (LGMD). Cells 2024, 13, 329. https://doi.org/10.3390/cells13040329.
- 2.
Angelini, C.; Giaretta, L.; Marozzo, R. An update on diagnostic options and considerations in limb-girdle dystrophies. Expert Rev. Neurother. 2018, 18, 693–703. https://doi.org/10.1080/14737175.2018.150899.
- 3.
Vissing, J. Limb girdle muscular dystrophies. Curr. Opin. Neurol. 2016, 29, 635–641. https://doi.org/10.1097/WCO.0000000000000375.
- 4.
Jokela, M.; Lehtinen, S.; Palmio, J.; et al. A novel COL6A2 mutation causing late-onset limb-girdle muscular dystrophy. J. Neurol. 2019, 266, 1649–1654. https://doi.org/10.1007/s00415-019-09307-y.
- 5.
Straub, V.; Murphy, A.; Udd, B.; et al. 229th ENMC international workshop: Limb girdle muscular dystrophies–nomenclature and reformed classification, Naarden, The Netherlands, 17–19 March 2017. Neuromuscul. Disord. 2018, 28, 702–710. https://doi.org/10.1016/j.nmd.2018.05.007.
- 6.
Angelini, C. LGMD. Identification, description and classification. Acta Myol. 2020, 39, 207–217. https://doi.org/10.36185/2532-1900-024.
- 7.
Turan, S.; Farruggio, A.P.; Srifa, W.; et al. Precise correction of disease mutations in induced pluripotent stem cells derived from patients with limb girdle muscular dystrophy. Mol. Ther. 2016, 24, 685–696. https://doi.org/10.1038/mt.2016.40.
- 8.
Thompson, R.; Straub, V. Limb-girdle muscular dystrophies—international collaborations for translational research. Nat. Rev. Neurol. 2016, 12, 294–309. https://doi.org/10.1038/nrneurol.2016.35.
- 9.
Iyadurai, S.J.P.; Kissel, J.T. The limb-girdle muscular dystrophies and the dystrophinopathies. Continuum 2016, 22, 1954–1977. https://doi.org/10.1212/CON.0000000000000406.
- 10.
Nicolau, S.; Liewluck, T. Autosomal Dominant Limb-Girdle Muscular Dystrophies. In: Principles and Practice of the Muscular Dystrophies; Springer International Publishing: Cham, Switzerland, 2024; pp. 73–91.
- 11.
Costa, R.; Rodia, M.T.; Fazzina, M.; et al. Transcriptomic and morphological characterization of a first Zebrafish model of Limb Girdle Muscular Dystrophy D2. In Proceedings of the 4th Italian Zebrafish Meeting, Palermo, Italy, 7–9 February 2024.
- 12.
Costa, R.; Rodia, M.T.; Vianello, S.; et al. Transportin 3 (TNPO3) and related proteins in limb girdle muscular dystrophy D2 muscle biopsies: A morphological study and pathogenetic hypothesis. Neuromuscul. Disord. 2020, 30, 685–692.
- 13.
Narayanaswami, P.; Liewluck, T. Principles and Practice of the Muscular Dystrophies; Springer International Publishing: Cham, Switzerland, 2023.
- 14.
Angelini, C.; Pegoraro, V.; Cenacchi, G. The clinical and molecular spectrum of autosomal dominant limb-girdle muscular dystrophies focusing on transportinopathy. Expert Opin. Orphan Drugs 2019, 7, 223–232.
- 15.
Gamez, J.; Navarro, C.; Andreu, A.L.; et al. Autosomal dominant limb-girdle muscular dystrophy: A large kindred with evidence for anticipation. Neurology 2001, 56, 450–454.
- 16.
Palenzuela, L.; Andreu, A.L.; Gamez, J.; et al. A novel autosomal dominant limb-girdle muscular dystrophy (LGMD 1F) maps to 7q32.1–32.2. Neurology 2003, 61, 404–406.
- 17.
Pál, E.; Zima, J.; Hadzsiev, K.; et al. A novel pathogenic variant in TNPO3 in a Hungarian family with limb-girdle muscular dystrophy 1F. Eur. J. Med. Genet. 2019, 62, 103662. https://doi.org/10.1016/j.ejmg.2019.103662.
- 18.
Vihola, A.; Palmio, J.; Danielsson, O.; et al. Novel mutation in TNPO3 causes congenital limb-girdle myopathy with slow progression. Neurol. Genet. 2019, 5, e337.
- 19.
Rodríguez, A.A.; Amayra, I.; García, I.; et al. Limb–girdle muscular dystrophy D2 TNPO3-related: A quality of life study. Muscles 2023, 2, 274–285.
- 20.
Costa, R.; Rodia, M.T.; Pacilio, S.; et al. LGMD D2 TNPO3-related: From Clinical spectrum to pathogenetic mechanism. Front. Neurol. 2022, 13, 840683. https://doi.org/10.3389/fneur.2022.840683.
- 21.
Angelini, C.; Rodríguez, A.A. Assessment of the quality of life in patients with LGMD. The case of transportinopathy. Acta Myol. 2024, 43,16–20. https//doi.org/10.36185/2532-1900-397.
- 22.
Angelini, C.; Marozzo, R.; Pinzan, E.; et al. A new family with transportinopathy: Increased clinical heterogeneity. Ther. Adv. Neurol. Disord. 2019, 12. https//doi.org/10.1177/1756286419850433.
This work is licensed under a Creative Commons Attribution 4.0 International License.
Suite 4002 Level 4, 447 Collins Street, Melbourne, Victoria 3000, Australia
General Inquiries: info@sciltp.com