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Journal of Neurology

, Volume 259, Issue 12, pp 2699–2706 | Cite as

Course and management of allogeneic stem cell transplantation in patients with mitochondrial neurogastrointestinal encephalomyopathy

  • Massimiliano FilostoEmail author
  • Mauro Scarpelli
  • Paola Tonin
  • Giovanna Lucchini
  • Fabio Pavan
  • Francesca Santus
  • Rossella Parini
  • Maria Alice Donati
  • Maria Sofia Cotelli
  • Valentina Vielmi
  • Alice Todeschini
  • Francesco Canonico
  • Giuliano Tomelleri
  • Alessandro Padovani
  • Attilio Rovelli
Original Communication

Abstract

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is an autosomal recessive disorder caused by mutations in the gene encoding thymidine phosphorylase (TP). Allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as a treatment for patients with MNGIE and a standardized approach to HSCT in this condition has recently been developed. We report on the transplant course, management and short-term follow-up in two MNGIE patients who underwent HSCT. The source of stem cells was bone marrow taken from an HLA 9/10 allele-matched unrelated donor in the first patient and from an HLA 10/10 allele-matched sibling donor in the second. Both patients achieved full donor chimerism, and we observed restoration of buffy coat TP activity and lowered urine nucleoside concentrations in both of them. The post-transplant clinical follow-up showed improvement in gastrointestinal dysmotility, abdominal cramps and diarrhea. Neurological assessment remained unchanged. However, the first patient died 15 months after HSCT due to gastrointestinal obstruction and shock; the second patient died 8 months after the procedure due to respiratory distress following septic shock. Although HSCT corrects biochemical abnormalities and improves gastrointestinal symptoms, the procedure can be risky in subjects already in poor medical condition as are many MNGIE patients. Since transplant-related morbidity and mortality increases with progression of the disease and number of comorbidities, MNGIE patients should be submitted to HSCT when they are still relatively healthy, in order to minimize the complications of the procedure. Anyway, there is still incomplete knowledge on the natural history of the disease in many affected patients and it is not yet clear when the best time to do a transplant is. Further clues to the therapeutic potential of HSCT could result from a prolonged observation in a greater number of non-transplanted and transplanted patients, which would allow us to answer the questions of if, how and when MNGIE patients require HSCT treatment.

Keywords

Allogeneic hematopoietic stem cell transplantation HSCT Mitochondrial neurogastrointestinal encephalomyopathy MNGIE Posterior reversible encephalopathy syndrome PRES 

Notes

Acknowledgments

All co-authors have read and agreed to the contents of this paper. We kindly thank Dr. Michio Hirano from the Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA for thymidine phosphorylase biochemical assay.

Conflicts of interest

The authors declare no conflicts of interest.

Ethical standard

The study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Massimiliano Filosto
    • 1
    Email author
  • Mauro Scarpelli
    • 2
  • Paola Tonin
    • 2
  • Giovanna Lucchini
    • 3
  • Fabio Pavan
    • 3
  • Francesca Santus
    • 3
  • Rossella Parini
    • 3
  • Maria Alice Donati
    • 4
  • Maria Sofia Cotelli
    • 1
  • Valentina Vielmi
    • 1
  • Alice Todeschini
    • 1
  • Francesco Canonico
    • 5
  • Giuliano Tomelleri
    • 2
  • Alessandro Padovani
    • 1
  • Attilio Rovelli
    • 3
  1. 1.Clinical Neurology, Section for Neuromuscular Diseases and NeuropathiesUniversity Hospital “Spedali Civili”BresciaItaly
  2. 2.Clinical Neurology, Department of Neurological, Neuropsychological, Morphological and Movement SciencesUniversity of VeronaVeronaItaly
  3. 3.Pediatric DepartmentMilano-Bicocca University, San Gerardo HospitalMonzaItaly
  4. 4.A. Meyer University Children’s HospitalFlorenceItaly
  5. 5.Department of RadiologySan Gerardo HospitalMonzaItaly

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