A new mutation in the TYMP-gene: clinical and morphological characteristics of a patient with MNGIE syndrome-Reference-Cited by-同舟云学术

A new mutation in the TYMP-gene: clinical and morphological characteristics of a patient with MNGIE syndrome

Published:2022-12-13 Issue:4 Volume:12 Page:56-72
ISSN:2413-0443
Container-title:Neuromuscular Diseases
language:
Short-container-title:Neuromuscular Diseases

Author:

Bardakov S. N.¹^ORCID,Limaev I. S.²,Emelin A. M.²^ORCID,Nikitins V.²,Presnyakov E. V.²,Kurbatov S. A.³^ORCID,Tsygankova P. G.⁴,Tsargush V. A.⁵^ORCID,Chekmareva I. A.⁶^ORCID,Kolmakova E. V.²^ORCID,Bakulina N. V.²,Deev R. V.⁷^ORCID

Affiliation:

1. S.M. Kirov Military Medical Academy, Ministry of Defense of Russia

2. North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of Russia

3. Scientific Research Institute of Experimental Biology and Medicine, Voronezh State Medical University named after N.N. Burdenko

4. Laboratory of Hereditary Metabolic Diseases of the Medical Genetic Research Center named after acad. N.P. Bochkov

5. Scientific and Practical Clinical Center for Diagnostics and Telemedicine Technologies of the Moscow Department of Health

6. National Medical Research Center for Surgery named after A.V. Vishnevsky, Ministry of Health of Russia

7. North-Western State Medical University named after I.I. Mechnikov, Ministry of Health of Russia; Human Stem Cell Institute

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.

Publisher

Publishing House ABV Press

Subject

Neurology (clinical),Neurology

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