Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE)

Kimberly A. Kripps, Warapan Nakayuenyongsuk, Brian J. Shayota, William Berquist, Natalia Gomez-Ospina, Carlos O. Esquivel, Waldo Concepcion, Jacinda B. Sampson, David J. Cristin, Whitney E. Jackson, Samuel Gilliland, Elizabeth A. Pomfret, Michael L. Kueht, Rowland W. Pettit, Youmna A. Sherif, Lisa T. Emrick, Sarah H. Elsea, Ryan Himes, Michio Hirano, Johan L.K. Van HoveFernando Scaglia, Gregory M. Enns, Austin A. Larson

Research output: Contribution to journalArticle

Abstract

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a fatal disorder characterized by progressive gastrointestinal dysmotility, peripheral neuropathy, leukoencephalopathy, skeletal myopathy, ophthalmoparesis, and ptosis. MNGIE stems from deficient thymidine phosphorylase activity (TP) leading to toxic elevations of plasma thymidine. Hematopoietic stem cell transplant (HSCT) restores TP activity and halts disease progression but has high transplant-related morbidity and mortality. Liver transplant (LT) was reported to restore TP activity in two adult MNGIE patients. We report successful LT in four additional MNGIE patients, including a pediatric patient. Our patients were diagnosed between ages 14 months and 36 years with elevated thymidine levels and biallelic pathogenic variants in TYMP. Two patients presented with progressive gastrointestinal dysmotility, and three demonstrated progressive peripheral neuropathy with two suffering limitations in ambulation. Two patients, including the child, had liver dysfunction and cirrhosis. Following LT, thymidine levels nearly normalized in all four patients and remained low for the duration of follow-up. Disease symptoms stabilized in all patients, with some manifesting improvements, including intestinal function. No patient died, and LT appeared to have a more favorable safety profile than HSCT, especially when liver disease is present. Follow-up studies will need to document the long-term impact of this new approach on disease outcome. Take Home Message: Liver transplantation is effective in stabilizing symptoms and nearly normalizing thymidine levels in patients with mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and may have an improved safety profile over hematopoietic stem cell transplant.

Original languageEnglish (US)
Pages (from-to)58-64
Number of pages7
JournalMolecular Genetics and Metabolism
Volume130
Issue number1
DOIs
StatePublished - May 2020
Externally publishedYes

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Keywords

  • Liver transplantation
  • Mitochondrial neurogastrointestinal encephalomyopathy
  • MNGIE
  • Thymidine
  • Thymidine phosphorylase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology

Cite this

Kripps, K. A., Nakayuenyongsuk, W., Shayota, B. J., Berquist, W., Gomez-Ospina, N., Esquivel, C. O., Concepcion, W., Sampson, J. B., Cristin, D. J., Jackson, W. E., Gilliland, S., Pomfret, E. A., Kueht, M. L., Pettit, R. W., Sherif, Y. A., Emrick, L. T., Elsea, S. H., Himes, R., Hirano, M., ... Larson, A. A. (2020). Successful liver transplantation in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Molecular Genetics and Metabolism, 130(1), 58-64. https://doi.org/10.1016/j.ymgme.2020.03.001