Mitochondrial Neurogastrointestinal Encephalomyopathy Disease (MNGIE)

Li, Shufang; Martí, Ramón; Hirano, Michio

doi:10.1007/978-3-030-05517-2_13

Cited by 4 publications

(9 citation statements)

References 120 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Even considering reference control values from other laboratories (634 ± 17 nmol/h/mg) ( Martí et al, 2004 ), residual activities of these subjects are higher than those of other late-onset MNGIE patients (16% of controls). Accordingly, plasma levels of thymidine (1.0 μmol/L) and deoxyuridine (1.7 μmol/L) assayed in Patient 1 were lower compared with mean values observed in late-onset MNGIE cases (thymidine: 1.4 ± 0.6 and deoxyuridine 2.3 ± 1.7 μmol/L) but still higher with respect to control (undetectable) ( Li et al, 2019 ).…”

Section: Discussionmentioning

confidence: 57%

TYMP Variants Result in Late-Onset Mitochondrial Myopathy With Altered Muscle Mitochondrial DNA Homeostasis

et al. 2020

View full text Add to dashboard Cite

Biallelic TYMP variants result in the mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), a juvenile-onset disorder with progressive course and fatal outcome. Milder late-onset (>40 years) form has been rarely described. Gene panel sequencing in a cohort of 60 patients featuring muscle accumulation of mitochondrial DNA (mtDNA) deletions detected TYMP defects in three subjects (5%), two of them with symptom onset in the fifth decade. One of the patients only displayed ptosis and ophthalmoparesis. Biochemical and molecular studies supported the diagnosis. Screening of TYMP is recommended in adult patients with muscle mtDNA instability, even in the absence of cardinal MNGIE features.

show abstract

Section: Discussionmentioning

confidence: 57%

TYMP Variants Result in Late-Onset Mitochondrial Myopathy With Altered Muscle Mitochondrial DNA Homeostasis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…И хотя в настоящее время отсутствуют данные об успешном лечении МНГИЭ, однако симптоматическое облегчение может быть достигнуто [3,11,12,14]. Используются препараты, повышающие активность дыхательной цепи (переносчики электронов), разнообразные кофакторы энзимных реакций энергетического обмена, антиокси-данты, средства, снижающие уровень лактатацидоза, и др.…”

Section: Discussionunclassified

“…Митохондриальные болезни (МБ) обусловлены генетическими и структурно-биохимическими дефектами, приводящими к нарушению тканевого дыхания. При МБ поражаются в первую очередь наиболее энергозависимые ткани и органы-мишени в различной комбинации: центральная нервная система, скелетная мускулатура, мышца сердца, органы зрения, почки, печень, костный мозг и эндокринная система [1][2][3].…”

unclassified

“…В настоящее время частота встречаемости МНГИЭ составляет 0,15 на 1 млн [3]. Средняя продолжительность жизни больного -37,6 года.…”

unclassified

“…Патогномоничных симптомов МНГИЭ нет. Частыми ее проявлениями являются [3,9,10] плазмы 56,5-41,0 г/л), преимущественно за счет альбумина (34,2-24,9 г/л). С марта 2020 г. отмечалось увеличение уровня аспартатаминотрансферазы до 88,6 Ед/л, аланинаминотрансферазы -до 133,3-56,9 Ед/л, лактатдегидрогеназы -до 730 Ед/л, креатинфосфокиназа -302 Ед/л, γ-глутамилтранспептидаза -124 Ед/л, D-димер -587-1482 нг/мг.…”

unclassified

See 2 more Smart Citations

Masks hiding mitochondrial neurogastrointestinal encephalomyopathy. Case report

Маев

Kolmakova²,

Бардаков³

et al. 2022

Terapevticheskii arkhiv

View full text Add to dashboard Cite

The first documented case of mitochondrial neurogastrointestinal encephalomyopathy was described in 1962 by R. Luft. The variety and am-biguity of the clinical manifestations of the disease complicate its early diagnosis and treatment. The first clinical manifestations of the disease are associated with the pathology of the gastrointestinal tract. Low alertness and insufficient awareness of doctors delays the timely diagnosis of mitochondrial neurogastrointestinal encephalomyopathy. The aim of the work is to increase the alertness and awareness of narrow specialties about the possibility of differential diagnosis of an extremely rare detected disease on the base of our clinical observation.

show abstract

A novel thymidine phosphorylase mutation in a family with Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Molecular docking, dynamic simulation and computational investigations

Ammar

Safi

Tlili

et al. 2022

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE; OMIM 603041) is a rare inherited metabolic disorder mostly caused by mutations in TYMP gene encoding thymidine phosphorylase (TP) protein that affects the mitochondrial nucleotide metabolism. TP, functionally active as a homodimer, is involved in the salvage pathway of pyrimidine nucleosides. MNGIE‐like syndrome having an overlapping phenotype of MNGIE was also described and has been associated with mutations in POLG and RRM2B genes. In the present study, we report the molecular investigation of a consanguineous family including two patients with clinical features suggestive of MNGIE syndrome. Bioinformatics analyses were carried out in addition to mtDNA deletion screening and copy number quantification in the blood of the two patients. Whole exome sequencing and Sanger sequencing analyses revealed the segregation in the affected family a novel mutation c.1205T>A (p.L402Q) within the exon 9 of the TYMP gene. In addition, mtDNA analysis revealed the absence of mtDNA deletions and a decrease of the copy number in the blood of the two patients of the studied family. The p.Leu402Gln mutation was located in a conserved amino acid within the α/β domain of the TP protein and several software supported its pathogenicity. In addition, and based on docking and molecular dynamic simulation analyses, results revealed that L402Q caused a conformational change in TP mutated structure and could therefore alter its flexibility and stability. These changes prevent also the formation of stable homodimer leading to non‐functional protein with partial or complete loss of its catalytic activity.

show abstract

Mitochondrial Neurogastrointestinal Encephalomyopathy Disease (MNGIE)

Cited by 4 publications

References 120 publications

TYMP Variants Result in Late-Onset Mitochondrial Myopathy With Altered Muscle Mitochondrial DNA Homeostasis

TYMP Variants Result in Late-Onset Mitochondrial Myopathy With Altered Muscle Mitochondrial DNA Homeostasis

Masks hiding mitochondrial neurogastrointestinal encephalomyopathy. Case report

A novel thymidine phosphorylase mutation in a family with Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE): Molecular docking, dynamic simulation and computational investigations

Contact Info

Product

Resources

About