Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE-MTDPS1)

doi:10.3390/jcm7110389

Review

. 2018 Oct 26;7(11):389.

doi: 10.3390/jcm7110389.

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE-MTDPS1)

Massimiliano Filosto¹, Stefano Cotti Piccinelli², Filomena Caria³, Serena Gallo Cassarino⁴, Enrico Baldelli⁵, Anna Galvagni⁶, Irene Volonghi⁷, Mauro Scarpelli⁸, Alessandro Padovani⁹

Affiliations

¹ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. massimiliano.filosto@unibs.it.
² Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. stefanocottipiccinelli@gmail.com.
³ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. cariafilomena@yahoo.it.
⁴ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. serena.gallocassarino@gmail.com.
⁵ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. enrico5589@gmail.com.
⁶ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. galvagni.anna@gmail.com.
⁷ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. irene.volonghi@hotmail.it.
⁸ Department of Neuroscience, Unit of Neurology, Azienda Ospedaliera Universitaria Integrata Verona, 37100 Verona, Italy. mscarpelli1980@libero.it.
⁹ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. alessandro.padovani@unibs.it.

PMID: 30373120
PMCID: PMC6262582
DOI: 10.3390/jcm7110389

Review

Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE-MTDPS1)

Massimiliano Filosto et al. J Clin Med. 2018.

. 2018 Oct 26;7(11):389.

doi: 10.3390/jcm7110389.

Authors

Massimiliano Filosto¹, Stefano Cotti Piccinelli², Filomena Caria³, Serena Gallo Cassarino⁴, Enrico Baldelli⁵, Anna Galvagni⁶, Irene Volonghi⁷, Mauro Scarpelli⁸, Alessandro Padovani⁹

Affiliations

¹ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. massimiliano.filosto@unibs.it.
² Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. stefanocottipiccinelli@gmail.com.
³ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. cariafilomena@yahoo.it.
⁴ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. serena.gallocassarino@gmail.com.
⁵ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. enrico5589@gmail.com.
⁶ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. galvagni.anna@gmail.com.
⁷ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. irene.volonghi@hotmail.it.
⁸ Department of Neuroscience, Unit of Neurology, Azienda Ospedaliera Universitaria Integrata Verona, 37100 Verona, Italy. mscarpelli1980@libero.it.
⁹ Center for Neuromuscular Diseases, Unit of Neurology, ASST Spedali Civili and University of Brescia, 25100 Brescia, Italy. alessandro.padovani@unibs.it.

PMID: 30373120
PMCID: PMC6262582
DOI: 10.3390/jcm7110389

Abstract

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE-MTDPS1) is a devastating autosomal recessive disorder due to mutations in TYMP, which cause a loss of function of thymidine phosphorylase (TP), nucleoside accumulation in plasma and tissues, and mitochondrial dysfunction. The clinical picture includes progressive gastrointestinal dysmotility, cachexia, ptosis and ophthalmoparesis, peripheral neuropathy, and diffuse leukoencephalopathy, which usually lead to death in early adulthood. Other two MNGIE-type phenotypes have been described so far, which are linked to mutations in POLG and RRM2B genes. Therapeutic options are currently available in clinical practice (allogeneic hematopoietic stem cell transplantation and carrier erythrocyte entrapped thymidine phosphorylase therapy) and newer, promising therapies are expected in the near future. Since successful treatment is strictly related to early diagnosis, it is essential that clinicians be warned about the clinical features and diagnostic procedures useful to suspect diagnosis of MNGIE-MTDPS1. The aim of this review is to promote the knowledge of the disease as well as the involved mechanisms and the diagnostic processes in order to reach an early diagnosis.

Keywords: MNGIE; MTDPS1; mitochondrial diseases; mitochondrial neurogastrointestinal encephalopathy; mitochondrial therapy.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Axial (A) and sagittal (B) brain MRI (magnetic resonance imaging) view shows marked leukoencephalopathy in a MNGIE (Mitochondrial Neurogastrointestinal Encephalomyopathy) subject.

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References

1. Nishino I., Spinazzola A., Hirano M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science. 1999;283:689–692. doi: 10.1126/science.283.5402.689. - DOI - PubMed
1. Viscomi C., Zeviani M. mMtDNA-maintenance defects: Syndromes and genes. J. Inherit. Metab. Dis. 2017;40:587–599. doi: 10.1007/s10545-017-0027-5. - DOI - PMC - PubMed
1. El-Hattab A.W., Scaglia F. SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic form with Methylmalonic Aciduria. In: Adam M.P., Ardinger H.H., Pagon R.A., Wallace S.E., Bean L.J.H., Stephens K., Amemiya A., editors. GeneReviews®. University of Washington; Seattle, WA, USA: 1993–2018. - PubMed
1. Nishino I., Spinazzola A., Papadimitriou A., Hammans S., Steiner I., Hahn C.D., Connolly A.M., Verloes A., Guimarães J., Maillard I., et al. Mitochondrial neurogastrointestinal encephalomyopathy: An autosomal recessive disorder due to thymidine phosphorylase mutations. Ann. Neurol. 2000;47:792–800. doi: 10.1002/1531-8249(200006)47:6<792::AID-ANA12>3.0.CO;2-Y. - DOI - PubMed
1. Spinazzola A., Marti R., Nishino I., Andreu A.L., Naini A., Tadesse S., Pela I., Zammarchi E., Donati M.A., Oliver J.A., et al. Altered thymidine metabolism due to defects of thymidine phosphorylase. J. Biol. Chem. 2002;277:4128–4133. doi: 10.1074/jbc.M111028200. - DOI - PubMed

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[1] Nishino I., Spinazzola A., Hirano M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science. 1999;283:689–692. doi: 10.1126/science.283.5402.689. - DOI - PubMed

[2] Nishino I., Spinazzola A., Hirano M. Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science. 1999;283:689–692. doi: 10.1126/science.283.5402.689. - DOI - PubMed

[3] Viscomi C., Zeviani M. mMtDNA-maintenance defects: Syndromes and genes. J. Inherit. Metab. Dis. 2017;40:587–599. doi: 10.1007/s10545-017-0027-5. - DOI - PMC - PubMed

[4] Viscomi C., Zeviani M. mMtDNA-maintenance defects: Syndromes and genes. J. Inherit. Metab. Dis. 2017;40:587–599. doi: 10.1007/s10545-017-0027-5. - DOI - PMC - PubMed

[5] El-Hattab A.W., Scaglia F. SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic form with Methylmalonic Aciduria. In: Adam M.P., Ardinger H.H., Pagon R.A., Wallace S.E., Bean L.J.H., Stephens K., Amemiya A., editors. GeneReviews®. University of Washington; Seattle, WA, USA: 1993–2018. - PubMed

[6] El-Hattab A.W., Scaglia F. SUCLA2-Related Mitochondrial DNA Depletion Syndrome, Encephalomyopathic form with Methylmalonic Aciduria. In: Adam M.P., Ardinger H.H., Pagon R.A., Wallace S.E., Bean L.J.H., Stephens K., Amemiya A., editors. GeneReviews®. University of Washington; Seattle, WA, USA: 1993–2018. - PubMed

[7] Nishino I., Spinazzola A., Papadimitriou A., Hammans S., Steiner I., Hahn C.D., Connolly A.M., Verloes A., Guimarães J., Maillard I., et al. Mitochondrial neurogastrointestinal encephalomyopathy: An autosomal recessive disorder due to thymidine phosphorylase mutations. Ann. Neurol. 2000;47:792–800. doi: 10.1002/1531-8249(200006)47:6<792::AID-ANA12>3.0.CO;2-Y. - DOI - PubMed

[8] Nishino I., Spinazzola A., Papadimitriou A., Hammans S., Steiner I., Hahn C.D., Connolly A.M., Verloes A., Guimarães J., Maillard I., et al. Mitochondrial neurogastrointestinal encephalomyopathy: An autosomal recessive disorder due to thymidine phosphorylase mutations. Ann. Neurol. 2000;47:792–800. doi: 10.1002/1531-8249(200006)47:6<792::AID-ANA12>3.0.CO;2-Y. - DOI - PubMed

[9] Spinazzola A., Marti R., Nishino I., Andreu A.L., Naini A., Tadesse S., Pela I., Zammarchi E., Donati M.A., Oliver J.A., et al. Altered thymidine metabolism due to defects of thymidine phosphorylase. J. Biol. Chem. 2002;277:4128–4133. doi: 10.1074/jbc.M111028200. - DOI - PubMed

[10] Spinazzola A., Marti R., Nishino I., Andreu A.L., Naini A., Tadesse S., Pela I., Zammarchi E., Donati M.A., Oliver J.A., et al. Altered thymidine metabolism due to defects of thymidine phosphorylase. J. Biol. Chem. 2002;277:4128–4133. doi: 10.1074/jbc.M111028200. - DOI - PubMed

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Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE-MTDPS1)

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Mitochondrial Neurogastrointestinal Encephalomyopathy (MNGIE-MTDPS1)

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Abstract

Conflict of interest statement

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Abstract

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