Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Pediatric Transplants

Allogeneic hematopoietic SCT for alpha-mannosidosis: an analysis of 17 patients

Bone Marrow Transplantation volume 47, pages 352–359 (2012)Cite this article

Abstract

Alpha-mannosidosis is a rare lysosomal storage disease. Hematopoietic SCT (HSCT) is usually recommended as a therapeutic option though reports are anecdotal to date. This retrospective multi institutional analysis describes 17 patients that were diagnosed at a median of 2.5 (1.1–23) years and underwent HSCT at a median of 3.6 (1.3–23.1) years. In all, 15 patients are alive (88%) after a median follow-up of 5.5 (2.1–12.6) years. Two patients died within the first 5 months after HSCT. Of the survivors, two developed severe acute GvHD (>=grade II) and six developed chronic GvHD. Three patients required re-transplantation because of graft failure. All 15 showed stable engraftment. The extent of the patients’ developmental delay before HSCT varied over a wide range. After HSCT, patients made developmental progress, although normal development was not achieved. Hearing ability improved in some, but not in all patients. We conclude that HSCT is a feasible therapeutic option that may promote mental development in alpha-mannosidosis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Stinchi S, Lullmann-Rauch R, Hartmann D, Coenen R, Beccari T, Orlacchio A et al. Targeted disruption of the lysosomal alpha-mannosidase gene results in mice resembling a mild form of human alpha-mannosidosis. Hum Mol Genet 1999; 8: 1365–1372.

    Article  CAS  Google Scholar 

  2. Michalski J, Haeuw J, Wieruszeski J, Montreuil J, Strecker G . In vitro hydrolysis of oligomannosyl oligosaccharides by the lysosomal alpha-d-mannosidases. Eur J Biochem 1990; 189: 369–379.

    Article  CAS  Google Scholar 

  3. Malm D, Nilssen O . Alpha-mannosidosis. Orphanet J Rare Dis 2008; 3: 21.

    Article  Google Scholar 

  4. Lyons MJ, Wood T, Espinoza L, Stensland HM, Holden KR . Early onset alpha-mannosidosis with slow progression in three Hispanic males. Dev Med Child Neurol 2007; 49: 854–857.

    Article  Google Scholar 

  5. Yunis JJ, Lewandowski RC, Sanfilippo SJ, Tsai MY, Foni I, Bruhl HH . Clinical manifestations of mannosidosis—a longitudinal study. Am J Med 1976; 61: 841–848.

    Article  CAS  Google Scholar 

  6. Berg T, Riise HMF, Hansen GM, Malm D, Tranebjærg L, Tollersrud OK et al. Spectrum of mutations in alpha-mannosidosis. Am J Hum Genet 1999; 64: 77–88.

    Article  CAS  Google Scholar 

  7. Wong LT, Vallance H, Savage A, Davidson AG, Applegarth D . Oral zinc therapy in the treatment of alpha-mannosidosis. Am J Med Genet 1993; 46: 410–414.

    Article  CAS  Google Scholar 

  8. Crawley AC, King B, Berg T, Meikle PJ, Hopwood JJ . Enzyme replacement therapy in alpha-mannosidosis guinea-pigs. Mol Genet Metab 2006; 89: 48–57.

    Article  CAS  Google Scholar 

  9. Blanz J, Stroobants S, Lullmann-Rauch R, Morelle W, Ludemann M, D′Hooge R et al. Reversal of peripheral and central neural storage and ataxia after recombinant enzyme replacement therapy in alpha-mannosidosis mice. Hum Mol Genet 2008; 17: 3437–3445.

    Article  CAS  Google Scholar 

  10. Vite CH, McGowan JC, Niogi SN, Passini MA, Drobatz KJ, Haskins ME et al. Effective gene therapy for an inherited CNS disease in a large animal model. Ann Neurol 2005; 57: 355–364.

    Article  CAS  Google Scholar 

  11. Walkley SU, Thrall MA, Dobrenis K, Huang M, March PA, Siegel DA et al. Bone marrow transplantation corrects the enzyme defect in neurons of the central nervous system in a lysosomal storage disease. Proc Natl Acad Sci USA 1994; 91: 2970–2974.

    Article  CAS  Google Scholar 

  12. Albert MH, Schuster F, Peters C, Schulze S, Pontz BF, Muntau AC et al. T-cell-depleted peripheral blood stem cell transplantation for alpha-mannosidosis. Bone Marrow Transplant 2003; 32: 443–446.

    Article  CAS  Google Scholar 

  13. Broomfield AA, Chakrapani A, Wraith JE . The effects of early and late bone marrow transplantation in siblings with alpha-mannosidosis. Is early haematopoietic cell transplantation the preferred treatment option? J Inherit Metab Dis 2010 Feb 18 (doi:10.1007/s10545-009-9035-4).

  14. Grewal SS, Shapiro EG, Krivit W, Charnas L, Lockman LA, Delaney KA et al. Effective treatment of α-mannosidosis by allogeneic hematopoietic stem cell transplantation. J Pediatr 2004; 144: 569–573.

    Article  CAS  Google Scholar 

  15. Wall DA, Grange DK, Goulding P, Daines M, Luisiri A, Kotagal S . Bone marrow transplantation for the treatment of alpha-mannosidosis. J Pediatr 1998; 133: 282–285.

    Article  CAS  Google Scholar 

  16. Will A, Cooper A, Hatton C, Sardharwalla IB, Evans DI, Stevens RF . Bone marrow transplantation in the treatment of alpha-mannosidosis. Arch Dis Child 1987; 62: 1044–1049.

    Article  CAS  Google Scholar 

  17. Aldenhofen M, Boelens J, DeKoenig TJ . The clinical outcome of Hurler syndrome after stem cell transplantation. Biol Blood Marrow Transplant 2008; 14: 485–498.

    Article  Google Scholar 

  18. Prasad VK, Kurtzberg J . Cord blood and bone marrow transplantation in inherited metabolic diseases: scientific basis, current status and future directions. Br J Haematol 2010; 148: 356–372.

    Article  Google Scholar 

  19. Yabe H, Inoue H, Matsumoto M, Hamanoue S, Hiroi A, Koike T et al. Unmanipulated HLA-haploidentical bone marrow transplantation for the treatment of fatal, nonmalignant diseases in children and adolescents. Int J Hematol 2004; 80: 78–82.

    Article  Google Scholar 

Download references

Acknowledgements

We would like to give our special thanks to all the patients and their parents who took part in this study. Moreover, we want to thank all the physicians and nurses that have been involved in the transplantation and the follow-up care and M Zimmermann for the help with statistical analysis. Our special gratitude goes to Mr J Forman and J Nobel from the ISMRD, who gave significant support to our study.

Author information

Authors and Affiliations

  1. Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany

    M Mynarek, C Klein & K-W Sykora

  2. Department of Pediatrics, Division of Hematology, University of Minnesota, Oncology, Blood and Marrow Transplantation, Minneapolis, MN, USA

    J Tolar & P J Orchard

  3. Department of Pediatric Hematology and Oncology, Ludwig Maximilians University, Munich, Germany

    M H Albert

  4. University of North Carolina at Chapel Hill, Program for Neurodevelopmental Function in Rare Disorders, Chapel Hill, NC, USA

    M L Escolar

  5. Department of Pediatrics: Stem Cell Transplantation Unit, University Medical Center Utrecht, Utrecht, The Netherlands

    J J Boelens

  6. Blood and Marrow Transplant Division, University of California San Francisco, Children's Hospital, San Francisco, CA, USA

    M J Cowan

  7. Great Ormond Street Hospital for Children NHS Trust, Metabolic Office, London, UK

    N Finnegan

  8. Department of Pediatrics, University Hospital Oslo, Oslo, Norway

    A Glomstein

  9. Department for Pediatric Bone Marrow Transplantation, Children's National Medical Center, Washington, DC, USA

    D A Jacobsohn

  10. Department of Pediatric Hematology, Charité University Medicine Berlin, Oncology and BMT, Berlin, Germany

    J S Kühl

  11. Department of Cell Transplantation and Regenerative Medicine, Tokai University School of Medicine, Shimokasuya, Isehara, Japan

    H Yabe

  12. Duke University Medical Center, The Pediatric Blood and Marrow Transplant Program, Durham, NC, USA

    J Kurtzberg

  13. Department of Gastroenterology, University Hospital of North Norway, Tromsoe, Norway

    D Malm

  14. Department of Neuropediatrics, Ruhr University Bochum, University Children's Hospital, Bochum, Germany

    T Lücke

Authors
  1. M Mynarek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J Tolar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M H Albert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M L Escolar
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J J Boelens
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M J Cowan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N Finnegan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. A Glomstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. D A Jacobsohn
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J S Kühl
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. H Yabe
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. J Kurtzberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. D Malm
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. P J Orchard
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. C Klein
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. T Lücke
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. K-W Sykora
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K-W Sykora.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mynarek, M., Tolar, J., Albert, M. et al. Allogeneic hematopoietic SCT for alpha-mannosidosis: an analysis of 17 patients. Bone Marrow Transplant 47, 352–359 (2012). https://doi.org/10.1038/bmt.2011.99

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2011.99

Keywords

This article is cited by

Search

Advanced search

Quick links