Skip to main content
SpringerLink
Log in

The effects of early and late bone marrow transplantation in siblings with alpha-mannosidosis. Is early haematopoietic cell transplantation the preferred treatment option?

  • Case Report
  • Published:
Journal of Inherited Metabolic Disease

Abstract

This article documents both the neurological and physical outcomes of the first published set of siblings undergoing transplantation at differing ages for α-mannosidosis. The older brother, the index case, was diagnosed at the age of 3 years and underwent transplantation at 13 years for the treatment of increasing somatic problems and recurrent infections. The younger brother had undergone transplantation pre-symptomatically at 6 months of age. Their clinical, radiological and developmental outcomes are documented and compared with the previous published cases, with the case for early transplantation being weighted against other potential therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Abbreviations

ERT:

enzyme replacement therapy

HCT:

haematopoietic cell transplantation

HLA:

human leukocyte antigen

MRI:

magnetic resonance imaging

CT:

computed tomography

MPS I:

mucopolysaccharidosis type 1

CNS:

central nervous system

References

  • Abraham D, Muir H, Olsen I, Winchester B (1985) Direct enzyme transfer from lymphocytes corrects a lysosomal storage disease. Biochem Biophys Res Commun 129:417–425

    Article  PubMed  CAS  Google Scholar 

  • Albert MH, Schuster F, Peters C et al (2003) T cell depleted peripheral blood stem cell transplantation for α-mannosidosis. Bone Marrow Transplant 32:443–446

    Article  PubMed  CAS  Google Scholar 

  • Ara JR, Mayayo E, Marzo ME, Guelbenzu S, Chabis A, Pina MA, Calderon C (1999) Neurological impairment in α-mannosidosis: a longitudinal clinical and MRI study of a brother and sister. Childs Nerv Syst 15:369–371

    Article  PubMed  CAS  Google Scholar 

  • Bahr BA, Bendiske J (2002) The neuropathogenic contributions of lysosomal dysfunction. J Neurochem 83:481–489

    Article  PubMed  CAS  Google Scholar 

  • Berg T, Riise HM, Hansen GM, Malm D, Tranebbjarg L, Tollersrud OK (1999) Spectrum of mutations in alpha-mannosidosis. Am J Hum Genet 64:77–88

    Article  PubMed  CAS  Google Scholar 

  • Blanz J, Stroobants S, Lullmann-Rauch R et al (2008) Reversal of peripheral and central neuronal storage and ataxia after recombinant enzyme replacement therapy in α-mannosidosis mice. Hum Mol Genet 17:3437–3445

    Article  PubMed  CAS  Google Scholar 

  • Boelens JJ, Wynn RF, O’Meara A et al (2007) Outcomes of hematopoietic stem cell transplantation for Hurler’s syndrome in Europe: a risk factor analysis for graft failure. Bone Marrow Transplant 40:225–233

    Article  PubMed  CAS  Google Scholar 

  • Chester MA, Lundblad A, Ockerman PA, Autio S (1982) Mannosidosis. In: Durand P, O’Brien JS (eds) Genetic errors in glycoprotein metabolism. Springer, Berlin, p 89

    Chapter  Google Scholar 

  • Clark GF, Patankar MS (1998) Response to a letter to Glyco-Forum entitled “Hypothesis: immunodeficiencies ina-mannosidosis, mycosis, AIDS and cancer—acommon mechanism of inhibition of the functionof the lectin interleukin 2 by oligomannosides”. Glycobiology 8:iii–iv

    Google Scholar 

  • Crawley AC, Walkley SU (2007) Developmental analysis of CNS pathology in the lysosomal storage disease α-mannosidosis. J Neuropathol Exp Neurol 66:687–697

    Article  PubMed  Google Scholar 

  • Dietmann JL, Flippi de la Palavesa MM, Tranchant C, Kastler B (1990) MR findings in mannosidosis. Neuroradiology 32:485–487, PMID 2287376

    Article  Google Scholar 

  • Dobrenis K (1992) Mechanisms underlying successful treatment of neuronal storage disease. Abstract 034 of the 7th International Congress of Inborn Errors of Metabolism, Vienna, Austria

  • Futerman AH, van Meer G (2004) The cell biology of lysosomal storage disorders. Nat Rev Mol Cell Biol 5:554–565

    Article  PubMed  CAS  Google Scholar 

  • Grewal SS, Shapiro EG, Krivit W et al (2004) Effective treatment of α-mannosidosis by allogeneic haematopoietic stem cell transplantation. J Pediatr 144:569–573

    Article  PubMed  CAS  Google Scholar 

  • Hansen MD, Filipovich AH, Davies SM et al (2008) Allogeneic hematopoietic cell transplantation (HCT) in Hurler’s syndrome using a reduced intensity preparative regimen. Bone Marrow Transplant 41:349–353

    Article  PubMed  CAS  Google Scholar 

  • Hickey WF, Kimura H (1998) Perivascular microglial cells of the CNS are bone derived and present in vivo. Science 239:290–292

    Article  Google Scholar 

  • Hoffmann B, Keshav S (2007) Gastrointestinal symptoms in Fabry disease: everything is possible, including treatment. Acta Paediatr Suppl 96:84–86, PMID 17391450

    Article  PubMed  Google Scholar 

  • Jeyakumar M, Dwek RA, Butters TD, Platt FM (2005) Storage solutions treating lysosomal disorders of the brain. Nat Rev Neurosci 6:713–725

    PubMed  Google Scholar 

  • Kakkis ED, Muenzer J, Tiller GE, Waber L et al (2001) Enzyme replacement therapy in mucopolysaccharidosis. N Eng J Med 344:1831–1888

    Article  Google Scholar 

  • Kennedy DW, Abkowitz JL (1997) Kinetics of central nervous system miroglial and macrophage engraftment: analysis using a transgenic bone marrow transplantation model. Blood 90:986–993

    PubMed  CAS  Google Scholar 

  • Kharbanda S, Panoskaltis-Moratari A, Haddad IY et al (2006) Inflammatory cytokines and the development of Pulmonary complications after allogeneic Hematopoietic Cell transplantation in patients with inherited metabolic storage disorders. Biol Blood Marrow Transplant 12:430–437

    Article  PubMed  CAS  Google Scholar 

  • Knoll RB, Kulkarni R, Netzloff ML (1986) Follow up of language and cognitive development in patients with mannosidosis. Arch Neurol 43:157–159

    Article  Google Scholar 

  • Malm D, Pantel J, Linaker OM (2005) Psychiatric symptoms in alpha-mannosidosis. J Intellect Disabil Res 49:865–871

    Article  PubMed  CAS  Google Scholar 

  • Miano M, Labopin M, Hartmann O et al (2007) Haematopoietic stem cell transplantation trends in children over the last three decades: a survey by the paediatric diseases working party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 39:89–99

    Article  PubMed  CAS  Google Scholar 

  • Michalski JC, Klein A (1999) Glycoprotein lysosomal storage disorders: α- and β-mannosidosis, fucosidosis and α-N-acetylgalactosaminidase deficiency. Biochem Biophys Acta 1455:69–84

    Article  PubMed  CAS  Google Scholar 

  • Mitchell ML, Erickson RP, Schmid D, Hieber V, Poznanski AK, Hicks SP (1981) Mannosidosis: two brothers with different degrees of disease severity. Clin Genet 20:191–202

    Article  PubMed  CAS  Google Scholar 

  • O’Brien T, Eastlund T, Peters C, Neglia JP, Defor T, Ramsay NKC, Baker KS (2004) Autoimmune haemolytic anaemia complicating haematopoietic cell transplantation in paediatric patients: high incidence and significant mortality in unrelated transplants for non-malignant diseases. Br J Haematol 127:67–75

    Article  PubMed  Google Scholar 

  • Peters CJ (2003) Effective treatment of the central nervous system in lysosomal storage diseases: save that brain. J Lab Clin Med 142:361–363

    Article  PubMed  Google Scholar 

  • Roces DP, Lüllmann-Rauch R, Peng J et al (2004) Efficacy of enzyme replacement therapy in α-mannosidosis mice: a preclinical animal study. Hum Mol Genet 13:1979–1988

    Article  PubMed  CAS  Google Scholar 

  • Spranger J, Gehler J, Cantz M (1976) The radiographic features of α-mannosidosis. Radiology 119:401

    PubMed  CAS  Google Scholar 

  • Staba SL, Escolar ML, Poe M et al (2004) Cord-blood transplants from unrelated donors in patients with Hurler’s syndrome. N Engl J Med 350:1932–1934

    Article  Google Scholar 

  • Sun H, Wolfe JH (2001) Recent progress in lysosomal α-mannosidosis and its deficiency. Exp Mol Med 33:1–7

    Article  PubMed  CAS  Google Scholar 

  • Thomas G (2001) Disorders of glycoprotein degradation: α-mannosidosis, β-mannosidosis, fucosidosis and sialidosis. In: Scriver CR, Beaudet AL, Sly WS, Valle D, Childs B, Kinzler KW, Vogelstein B (eds) The metabolic and molecular bases of inherited metabolic disease, 8th edn. McGraw-Hill Medical, pp 3507–3516

  • Vite CH, McGowan JC, Niogi SN, Passini MA, Drobatz KJ, Haskins ME, Wolfe JH (2005) Effective gene therapy for an inherited metabolic disease in a large animal model. Ann Neurol 57:355–364

    Article  PubMed  CAS  Google Scholar 

  • Walkley SU (2004) Pathogenic cascades and brain dysfunction. In: Platt FM, Walkley SU (eds) Lysosomal disorders of the brain. Oxford University Press, New York, p 290–324

    Chapter  Google Scholar 

  • Walkley SU (2007) Pathological mechanisms in lysosomal disease: a reappraisal of the role of the lysosome. Acta Paediatr 96:26–32

    Article  Google Scholar 

  • Walkley SU, Dobrenis K (1995) Bone marrow transplantation for the treatment of lysosomal storage disorders. Lancet 345:1398–1402

    Article  Google Scholar 

Download references

Acknowledgements

The authors thank Dr. Stensland, Senior Scientist, Department of Medical Genetics, University Hospital of Northern Norway, Breivika, Tromsø, Norway, for her work on the identification of the mutation in these patients.

Author information

Authors and Affiliations

  1. Department of Genetic Medicine, Royal Manchester Children’s Hospital, Manchester, UK

    A. A. Broomfield & J. E. Wraith

  2. Birmingham Children’s Hospital, Birmingham, UK

    A. Chakrapani

  3. Department of Metabolic Disease, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London, WC1N 3JH, UK

    A. A. Broomfield

Authors
  1. A. A. Broomfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Chakrapani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. E. Wraith
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. A. Broomfield.

Additional information

Communicated by: Olaf Bodamer

Competing interest: None declared

Rights and permissions

Reprints and permissions

About this article

Cite this article

Broomfield, A.A., Chakrapani, A. & Wraith, J.E. 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 33 (Suppl 3), 123–127 (2010). https://doi.org/10.1007/s10545-009-9035-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10545-009-9035-4

Keywords

Search

Navigation