Liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE): clinical long-term follow-up and pathogenic implications
Abstract
We report the longest follow-up of clinical and biochemical features of two previously reported adult mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) patients treated with liver transplantation (LT), adding information on a third, recently transplanted, patient. All three patients overcame the early post-operative period and tolerated immunosuppressive therapy. Plasma nucleoside levels dramatically decreased, with evidence of clinical improvement of ambulation and neuropathy. Conversely, other features of MNGIE, as gastrointestinal dysmotility, low weight, ophthalmoparesis, and leukoencephalopathy were essentially unchanged. A similar picture characterized two patients treated with allogenic hematopoietic stem cell transplantation (AHSCT). In conclusion, LT promptly and stably normalizes nucleoside imbalance in MNGIE, stabilizing or improving some clinical parameters with marginal periprocedural mortality rate as compared to AHSCT. Nevertheless, restoring thymidine phosphorylase (TP) activity, achieved by both LT and AHSCT, does not allow a full clinical recovery, probably due to consolidated cellular damage and/or incomplete enzymatic tissue replacement.
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Disease-modifying strategies such as allogeneic stem cell transplantation, liver transplantation, and experimental gene therapy approaches aim to correct thymidine phosphorylase deficiency and may alter trajectory in selected patients with MNGIE.
“Case series and mechanistic studies highlight the importance of early recognition, as disease-modifying strategies such as allogeneic stem cell transplantation, liver transplantation, and experimental gene therapy approaches aim to correct thymidine phosphorylase deficiency and may alter trajectory in selected patients (D’Angelo et al., 2020; Filosto et al., 2012; Habibzadeh et al., 2020; Yadak et”
From Autonomic nervous system and gastrointestinal manifestations with an emphasis on gastric dysfunction (2026) · cites this paper as D’Angelo et al., 2020
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- Authors
- D’Angelo, R., Boschetti, E., Amore, G., Costa, R., Pugliese, A., Caporali, L., Gramegna, L. L., Papa, V., Vizioli, L., Capristo, M., Contin, M., Mohamed, S., Cenacchi, G., Lodi, R., Morelli, M. C., Fasano, L., Pisani, L., Cescon, M., Tonon, C., Pinna, A. D., Dotti, M. T., Sicurelli, F., Scarpelli, M., Filosto, M., Casali, C., Pironi, L., Carelli, V., De Giorgio, R., & Rinaldi, R.
- Affiliations
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- University of Bologna (IT)
- University of Messina (IT)
- Istituto delle Scienze Neurologiche di Bologna (IT)
- University of Siena (IT)
- University of Verona (IT)
- Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT)
- Sapienza University of Rome (IT)
- Corresponding author
- D’Angelo, Roberto
- ORCID
- D’Angelo, Roberto
- Boschetti, Elisa
- Amore, Giulia
- Costa, Roberta
- Pugliese, Alessia
- Caporali, Leonardo
- Gramegna, Laura Ludovica
- Papa, Valentina
- Capristo, Mariantonietta
- Contin, Manuela
- Mohamed, Susan
- Cenacchi, Giovanna
- Lodi, Raffaele
- Morelli, Maria Cristina
- Fasano, Luca
- Pisani, Lara
- Cescon, Matteo
- Tonon, Caterina
- Pinna, Antonio Daniele
- Dotti, Maria Teresa
- Filosto, Massimiliano
- Casali, Carlo
- Pironi, Loris
- Rinaldi, Rita
- Venue
- Journal of Neurology
- Published
- 2020-07-18
- Volume
- 267
- Issue
- 12
- Pages
- 3702-3710
- ISSN
- 0012-1037 (ISSN-L)
- 0340-5354
- 1432-1459
- OpenAlex
- W3042925610
- Cited by
- 29
- References
- 25
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 6 · 2021: 4 · 2020: 1
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- mitochondrial neurogastrointestinal encephalomyopathy, liver transplantation, allogeneic hematopoietic stem cell transplantation, thymidine phosphorylase, immunosuppressive therapy, long-term follow-up, neuropathy, gastrointestinal motility disorders, leukoencephalopathy, ophthalmoparesis, periprocedural mortality
- MeSH terms
- Adult, Follow-Up Studies, Humans, Ophthalmoplegia, Thymidine Phosphorylase, Liver Transplantation, Mitochondrial Encephalomyopathies
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