Article
Biochemistry & Molecular Biology
Helia Mojtabavi, Farzad Fatehi, Sepideh Shahkarami, Nima Rezaei, Shahriar Nafissi
Summary: MNGIE is a multi-system disorder caused by TYMP gene mutations, with affected Iranian patients diagnosed between the ages of 18 and 49. This study identified five novel mutations in the TYMP gene, confirming the autosomal recessive inheritance pattern of MNGIE in the Iranian population.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2021)
Article
Clinical Neurology
Elena Bonora, Sanjiban Chakrabarty, Georgios Kellaris, Makiko Tsutsumi, Francesca Bianco, Christian Bergamini, Farid Ullah, Federica Isidori, Irene Liparulo, Chiara Diquigiovanni, Luca Masin, Nicola Rizzardi, Mariapia Giuditta Cratere, Elisa Boschetti, Valentina Papa, Alessandra Maresca, Giovanna Cenacchi, Rita Casadio, Pierluigi Martelli, Ivana Matera, Isabella Ceccherini, Romana Fato, Giuseppe Raiola, Serena Arrigo, Sara Signa, Angela Rita Sementa, Mariasavina Severino, Pasquale Striano, Chiara Fiorillo, Tsuyoshi Goto, Shumpei Uchino, Yoshinobu Oyazato, Hisayoshi Nakamura, Sushil K. Mishra, Yu-Sheng Yeh, Takema Kato, Kandai Nozu, Jantima Tanboon, Ichiro Morioka, Ichizo Nishino, Tatsushi Toda, Yu-ichi Goto, Akira Ohtake, Kenjiro Kosaki, Yoshiki Yamaguchi, Ikuya Nonaka, Kazumoto Iijima, Masakazu Mimaki, Hiroki Kurahashi, Anja Raams, Alyson MacInnes, Mariel Alders, Marc Engelen, Gabor Linthorst, Tom de Koning, Wilfred den Dunnen, Gerard Dijkstra, Karin van Spaendonck, Dik C. van Gent, Eleonora M. Aronica, Paolo Picco, Valerio Carelli, Marco Seri, Nicholas Katsanis, Floor A. M. Duijkers, Mariko Taniguchi-Ikeda, Roberto De Giorgio
Summary: Variants in the LIG3 gene result in a mitochondrial disease characterized by predominant gut dysmotility, encephalopathy, and neuromuscular abnormalities. Defects in the LIG3 gene affect mtDNA maintenance and lead to mtDNA depletion.
Article
Nutrition & Dietetics
Ana Barisic, Dina Ljubas Kelecic, Darija Vranesic Bender, Irena Karas, Marko Brinar, Vladimir Miletic, Zeljko Krznaric
Summary: In this study, we reported on a female patient diagnosed with MNGIE who received early and aggressive total parenteral nutrition supervised by an experienced nutritional team. The findings suggest that adequate nutritional support, particularly parenteral nutrition, may prolong the lifespan of patients with MNGIE.
FRONTIERS IN NUTRITION
(2022)
Article
Genetics & Heredity
A. Paisiou, M. Rogalidou, R. Pons, E. Ioannidou, K. Dimakou, A. Papadopoulou, F. M. Vaz, G. Vessalas, S. M. Goorden, J. Roelofsen, A. Zoetekouw, M. M. Nieman, E. Dimitriou, M. Moraitou, I Peristeri, H. Michelakakis, A. B. P. van Kuilenburg
Summary: A Greek female patient with the Classic form of the rare disorder Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) underwent allogeneic hematopoietic stem cell transplantation, resulting in significant decreases in plasma thymidine and deoxyuridine levels, increased thymidine phosphorylase activity, stabilized disease symptoms, and some improvement observed in neurological and gastrointestinal symptoms. Further follow up studies are needed to determine the long term impact.
MOLECULAR GENETICS AND METABOLISM REPORTS
(2022)
Article
Oncology
Guelcihan Ozek, Serap Aksoylar, Sema Kalkan Ucar, Ebru Canda, Mediha Akcan, Ozgur Carti, Zuhal Onder Sivis, Yesim Oymak, Havva Yazici, Bridget Bax, Fatma Derya Bulut, Merve Yoldas Celik, Fehime Erdem, Mahmut Coker, Savas Kansoy
Summary: In this retrospective study, the effectiveness of reduced toxicity myeloablative conditioning regimen in hematopoietic stem cell transplantation (HSCT) for mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients was evaluated. Results showed that the Treosulfan-based regimen was well tolerated, although engraftment failure is a significant concern.
PEDIATRIC BLOOD & CANCER
(2023)
Review
Clinical Neurology
Renae J. Stefanetti, Yi Shiau Ng, Linda Errington, Alasdair P. Blain, Robert McFarland, Grainne S. Gorman
Summary: Managing stroke-like episodes in patients with mitochondrial disease is challenging, and a systematic review on the use of L-arginine in this context revealed no demonstrable clinical benefit in either acute or prophylactic treatment. More robust controlled trials are needed to assess the efficacy and safety profile of L-arginine.
Article
Biotechnology & Applied Microbiology
Marta Pares, Cristina Fornaguera, Ferran Vila-Julia, Sejin Oh, Steven H. Y. Fan, Ying K. Tam, Natalia Comes, Francisco Vidal, Ramon Marti, Salvador Borros, Jordi Barquinero
Summary: This study demonstrated the successful integration of a TYMP transgene into hepatocytes in a murine model of MNGIE using CRISPR/Cas9 and TYMP cDNA. The best in vivo results were obtained with LNP delivering CRISPR/Cas9 mRNA, showing long-term reduction in plasma nucleoside levels. Editing the Tymp and Alb loci resulted in transgene expression and functional enzyme production in liver cells, highlighting the potential of liver-directed genome editing for correcting MNGIE.
HUMAN GENE THERAPY
(2021)
Article
Gastroenterology & Hepatology
Neethi Dasu, Brian Blair, C. Jonathan Foster, Colin Smith
Summary: This article presents a unique case of a 24-year-old male who was admitted for intractable nausea, emesis, weight loss, and abdominal discomfort. The patient was diagnosed with mitochondrial neurogastrointestinal encephalopathy after undergoing an extensive workup. Early diagnosis is crucial for the proper management of this complex disease, and this case provides clinicians with a better understanding and management approach.
CASE REPORTS IN GASTROINTESTINAL MEDICINE
(2022)
Review
Endocrinology & Metabolism
Michio Hirano, Valerio Carelli, Roberto De Giorgio, Loris Pironi, Anna Accarino, Giovanna Cenacchi, Roberto D'Alessandro, Massimiliano Filosto, Ramon Marti, Francesco Nonino, Antonio Daniele Pinna, Elisa Baldin, Bridget Elizabeth Bax, Alessio Bolletta, Riccardo Bolletta, Elisa Boschetti, Matteo Cescon, Roberto D'Angelo, Maria Teresa Dotti, Carla Giordano, Laura Ludovica Gramegna, Michelle Levene, Raffaele Lodi, Hanna Mandel, Maria Cristina Morelli, Olimpia Musumeci, Alessia Pugliese, Mauro Scarpelli, Antonio Siniscalchi, Antonella Spinazzola, Galit Tal, Javier Torres-Torronteras, Luca Vignatelli, Irina Zaidman, Heinz Zoller, Rita Rinaldi, Massimo Zeviani
Summary: MNGIE is a rare autosomal recessive disease caused by TYMP mutations, leading to gastrointestinal and neurological symptoms. Diagnosis is challenging and treatment options are limited, with a need for standardized monitoring methods.
JOURNAL OF INHERITED METABOLIC DISEASE
(2021)
Review
Genetics & Heredity
Heng Wang, Gechong Ruan, Shan Yang, Hui Li, Zixi Sun, Bowen Tian, Pengguang Yan, Yue Li, Hong Yang, Yong Zhong, Jiaming Qian
Summary: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare disorder characterized by gastrointestinal and neurological symptoms. This study reports the case of a 33-year-old male diagnosed with MNGIE based on a novel pathogenic variant in the TYMP gene. Ophthalmic examinations revealed inner retina thinning, decreased amplitudes in electroretinogram (ERG), and specific optic nerve abnormalities observed for the first time in MNGIE.
AMERICAN JOURNAL OF MEDICAL GENETICS PART A
(2023)
Review
Biology
Eugenia Borgione, Mariangela Lo Giudice, Sandro Santa Paola, Marika Giuliano, Francesco Domenico Di Blasi, Vincenzo Di Stefano, Antonino Lupica, Filippo Brighina, Rosa Pettinato, Corrado Romano, Carmela Scuderi
Summary: This article describes a novel homoplasmic m.7484A>G mutation in the tRNA(Ser(UCN)) gene, leading to profound intellectual disability, spastic tetraplegia, sensorineural hearing loss, and typical clinical manifestations of MELAS syndrome in a girl. The same mutation was also found in the mother, causing mild cognitive deficit, cerebellar ataxia, myoclonic epilepsy, sensorineural hearing loss, and myopathy consistent with MERRF syndrome. This is the first anticodon mutation in the tRNA(Ser(UCN)) and the second homoplasmic mutation in the anticodon triplet reported to date.
Article
Biochemistry & Molecular Biology
Mark Mencias, Michelle Levene, Kevin Blighe, Bridget E. Bax
Summary: This study identified a plasma and/or serum miRNA biomarker panel that can robustly distinguish between MNGIE patients and healthy controls, with certain miRNAs showing upregulation in MNGIE. It also observed a reduction in longitudinal miRNA expression of miR-34a-5p in patients treated with EE-TP, correlating with biochemical and clinical improvements.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Daniele Orsucci, Elena Caldarazzo Ienco, Vincenzo Montano, Gabriele Siciliano, Michelangelo Mancuso
Summary: MELAS is a rare inherited mitochondrial disease associated with severe multiorgan involvement and stress-induced metabolic derangements; currently, there are no etiopathogenetic therapies for stroke-like episodes, with treatment mainly relying on anti-epileptic drugs and supportive therapy.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Medicine, General & Internal
Igor V. Maev, Elena V. Kolmakova, Sergey N. Bardakov, Roman V. Deev, Yuri A. Krivolapov, Inna E. Kotkas, Elena A. Manushina, Sergei A. Kurbatov, Polina G. Tsygankova, Alexey M. Emelin, Natalia V. Bakulina
Summary: The first documented case of mitochondrial neurogastrointestinal encephalomyopathy was described in 1962, characterized by a variety and ambiguity of clinical manifestations, complicating its early diagnosis and treatment. Low alertness and insufficient awareness of doctors delay the timely diagnosis of the disease. The aim of this work is to increase the alertness and awareness of narrow specialties regarding the possibility of differential diagnosis of this extremely rare detected disease based on our clinical observation.
TERAPEVTICHESKII ARKHIV
(2022)
Article
Dermatology
Janan Mohamad, Ofer Sarig, Paula Beattie, Kiril Malovitski, Sari Assaf, Edel O'Toole, Janice Schwartz, Holly Evans, Liat Samuelov, Eli Sprecher
Summary: This study reports on a novel clinical phenotype resulting from germline mosaicism for a large genomic deletion spanning six keratin genes. The genomic variant leads to a truncated form of keratin 17, which disrupts keratinocyte cell cytoskeleton formation in vitro.
BRITISH JOURNAL OF DERMATOLOGY
(2022)