Email this article A new mutation in the TYMP-gene: clinical and morphological characteristics of a patient with MNGIE syndrome
- Authors: Bardakov S.N.1, Limaev I.S.2, Emelin A.M.2, Nikitins V.2, Presnyakov E.V.2, Kurbatov S.A.3, Tsygankova P.G.4, Tsargush V.A.5, Chekmareva I.A.6, Kolmakova E.V.2, Bakulina N.V.2, Deev R.V.2,7
-
Affiliations:
- S.M. Kirov Military Medical Academy, Ministry of Defense of Russia
- North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of Russia
- Scientific Research Institute of Experimental Biology and Medicine, Voronezh State Medical University named after N.N. Burdenko
- Laboratory of Hereditary Metabolic Diseases of the Medical Genetic Research Center named after acad. N.P. Bochkov
- Scientific and Practical Clinical Center for Diagnostics and Telemedicine Technologies of the Moscow Department of Health
- National Medical Research Center for Surgery named after A.V. Vishnevsky, Ministry of Health of Russia
- Human Stem Cell Institute
- Issue: Vol 12, No 4 (2022)
- Pages: 56-72
- Section: ORIGINAL REPORTS
- Published: 13.12.2022
- URL: https://nmb.abvpress.ru/jour/article/view/509
- DOI: https://doi.org/10.17650/2222-8721-2022-12-4-56-72
- ID: 509
Cite item
Full Text
Abstract
Mitochondrial neurogastrointestinal encephalomyopathy is an extremely rare (1–9:1 000 000, Orphanet, 2021) multisystem genetic disease caused by mutations in the TYMP gene encoding the enzyme thymidine phosphorylase.
The article presents the data of a thirteen‑year survey on 40‑year‑old patient D. with clinical manifestations of mitochondrial neurogastrointestinal encephalomyopathy syndrome associated with the previously undescribed missense mutation c.1301G>T (p.Gly434Val) of the TYMP gene. Detailed clinical picture (gastrointestinal dysfunction, cachexia, blepharoptosis, ophthalmoparesis, peripheral polyneuropathy and leukoaraiosis), electroneuromyography data (demyelination with secondary axonopathy), high blood serum level of dihydrothymine together with normal levels of thymidine and deoxyuridine made it possible to verify the diagnosis. Histopathological examination revealed atrophy of the longitudinal (outer) muscle layer of the small and large intestines and a significant decrease in the number of CD117+ cells (telocytes), signs of damage to the striated skeletal muscles of a mixed nature with a predominance of the myogenic pattern, as well the destruction of the myelin sheaths of peripheral nerves. Histochemical examination did not reveal “ragged red fibers” characteristic of mitochondrial pathology. Transmission electron microscopy demonstrated the presence of megalomitochondria in the myocardium.
About the authors
S. N. Bardakov
S.M. Kirov Military Medical Academy, Ministry of Defense of Russia
Author for correspondence.
Email: epistaxis@mail.ru
ORCID iD: 0000-0002-3804-6245
Sergey Nikolaevich Bardakov
6 Akademika Lebedeva St., Saint Petersburg 194044
Russian FederationI. S. Limaev
North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of Russia
Email: fake@neicon.ru
41 Kirochnaya St., Saint Petersburg 191123
Russian FederationA. M. Emelin
North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of Russia
Email: fake@neicon.ru
ORCID iD: 0000-0003-4109-0105
41 Kirochnaya St., Saint Petersburg 191123
Russian FederationV. Nikitins
North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of Russia
Email: fake@neicon.ru
41 Kirochnaya St., Saint Petersburg 191123
Russian FederationE. V. Presnyakov
North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of Russia
Email: fake@neicon.ru
41 Kirochnaya St., Saint Petersburg 191123
Russian FederationS. A. Kurbatov
Scientific Research Institute of Experimental Biology and Medicine, Voronezh State Medical University named after N.N. Burdenko
Email: fake@neicon.ru
ORCID iD: 0000-0002-8886-5222
10 Studencheskaya St., Voronezh 394622
Russian FederationP. G. Tsygankova
Laboratory of Hereditary Metabolic Diseases of the Medical Genetic Research Center named after acad. N.P. Bochkov
Email: fake@neicon.ru
1 Moskvorechye St., Moscow 115478
Russian FederationV. A. Tsargush
Scientific and Practical Clinical Center for Diagnostics and Telemedicine Technologies of the Moscow Department of Health
Email: fake@neicon.ru
ORCID iD: 0000-0002-5459-986X
Build. 1, 24 Petrovka St., Moscow 127051
Russian FederationI. A. Chekmareva
National Medical Research Center for Surgery named after A.V. Vishnevsky, Ministry of Health of Russia
Email: fake@neicon.ru
ORCID iD: 0000-0003-0126-4473
27 Bolshaya Serpukhovskaya St., Moscow 115093
Russian FederationE. V. Kolmakova
North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of Russia
Email: fake@neicon.ru
ORCID iD: 0000-0002-1745-6982
41 Kirochnaya St., Saint Petersburg 191123
Russian FederationN. V. Bakulina
North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of Russia
Email: fake@neicon.ru
41 Kirochnaya St., Saint Petersburg 191123
Russian FederationR. V. Deev
North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of Russia; Human Stem Cell Institute
Email: fake@neicon.ru
ORCID iD: 0000-0001-8389-3841
41 Kirochnaya St., Saint Petersburg 191123
3 Gubkina St., Moscow 119333
Russian FederationReferences
Supplementary files
