Skip to main content
SpringerLink
Log in

Blutstammzelltransplantation bei Mukopolysaccharidose Typ 1H (Morbus Hurler)

Klinischer Verlauf und Rückbildung intrakranialer Veränderungen

Stem cell transplantation (SCT) in children with mucopolysaccharidosis type 1 (MPS 1H, Hurler syndrome)

Neuropsychological development and regression of intracranial lesions

  • Originalien
  • Published:
Monatsschrift Kinderheilkunde Aims and scope Submit manuscript

Zusammenfassung

Das Hurler-Syndrom (MPS 1H) ist eine progressive, autosomal-rezessiv vererbte Erkrankung der Mukopolysaccharide, die zu verminderter Lebensqualität und vorzeitigem Tod führt. Die präsentierten beiden Kasuistiken belegen den günstigen Verlauf der psychomotorischen Entwicklung bei Kindern mit MPS 1H nach Blutstammzelltransplantation (BSCT). Die intrakranialen, durch MRT nachgewiesenen Veränderungen—multiple fokale Läsionen und ausgeprägter Hydrozephalus—waren nach BSCT rückläufig. Zum Zeitpunkt der BSCT, die im Alter von 19 bzw. 32 Monaten durchgeführt wurde, wiesen beide Kinder eine psychomotorische Retardierung auf und zeigten die typischen Stigmata des Hurler-Syndroms. Aktuell sind beide Patienten in ambulanter Betreuung, eine Graft-versus-host-disease (GvHD) wurde nicht gesehen. Sie haben eine stabile Transplantatfunktion ohne rezidivierende Infektionen wie vor BSCT.

Schlussfolgerung

Die psychomotorische Entwicklung macht bei beiden Kindern Fortschritte. Die BSCT ist Therapie der Wahl für Kinder mit einer MPS 1H. Fehlt ein HLA-identischer Familien-/ Fremdspender, kann die HLA-haploidentische BSCT erwogen werden.

Abstract

Hurler syndrome (MPS 1H) is a progressive autosomal recessive inborn error of mucopolysaccharide metabolism leading to a decreased quality of life and premature death. Two case reports are presented to demonstrate the favorable course of psychomotor development in children with MPS 1H after peripheral blood stem cell transplantation (BSCT). Magnetic resonance imaging (MRI) scans of the brain illustrate the regression of intracranial lesions after BSCT. The children received BSCT from their mothers at the age of 19 and 32 months, respectively. At the time of BSCT, both patients showed psychomotor retardation and the typical stigmata of Hurler syndrome. Today, both patients are in ambulatory care, and graft-versus-host disease (GVHD) was not seen. They show stable graft function, without recurrent infections as prior to BSCT. Psychomotor development is improving in both children.

Conclusion

BSCT is the therapy of choice for children with MPS 1H. In the absence of a matched family or matched unrelated donor, HLA-haploidentical BSCT can be considered.

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.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3
Abb. 4
Abb. 5
Abb. 6
Abb. 7
Abb. 8

Abbreviations

BSCT:

Blutstammzelltransplantation

GvHD:

Graft-versus-host-disease (Transplantat-gegen-Wirt-Krankheit)

MPS:

Mukopolysaccharidose

Literatur

  1. Aversa F, Tabilio A, Velardi A et al. (1998) Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 339:1186–1193

    Article  CAS  PubMed  Google Scholar 

  2. Baxter MA, Wynn RF, Deakin JA et al. (2002) Retrovirally mediated correction of bone marrow-derived mesenchymal stem cells from patients with mucopolysaccharidosis type I. Blood 99:1857–1859

    Article  PubMed  Google Scholar 

  3. Beck M (2001) Variable clinical presentation in lysosomal storage disorders. J Inherit Metab Dis (Suppl 2) 24:47–51

    Google Scholar 

  4. Dangel JH (1998) Cardiovascular changes in children with mucopolysaccharide storage diseases and related disorders—clinical and echocardiographic findings in 64 patients. Eur J Pediatr 157:534–538

    Article  CAS  PubMed  Google Scholar 

  5. Field RE, Buchanan JA, Copplemans MG et al. (1994) Bone-marrow transplantation in Hurler’s syndrome. Effect on skeletal development. J Bone Joint Surg Br 76:975–981

    CAS  PubMed  Google Scholar 

  6. Fratantoni JC, Hall CW, Neufeld EF (1968) The defect in Hurler’s and Hunter’s syndromes: faulty degradation of mucopolysaccharide. Proc Natl Acad Sci USA 60:699–706

    CAS  PubMed  Google Scholar 

  7. Gaipa G, Dassi M, Perseghin P et al. (2003) Allogeneic bone marrow stem cell transplantation following CD34+ immunomagnetic enrichment in patients with inherited metabolic storage diseases. Bone Marrow Transplant 31:857–860

    Article  CAS  PubMed  Google Scholar 

  8. Grewal SS, Krivit W, Defor TE et al. (2002) Outcome of second hematopoietic cell transplantation in Hurler syndrome. Bone Marrow Transplant 29:491–496

    Article  CAS  PubMed  Google Scholar 

  9. Guffon N, Souillet G, Maire I et al. (1998) Follow-up of nine patients with Hurler syndrome after bone marrow transplantation. J Pediatr 133:119–125

    CAS  PubMed  Google Scholar 

  10. Handgretinger R, Schumm M, Lang P et al. (1999) Transplantation of megadoses of purified haploidentical stem cells. Ann N Y Acad Sci 872:351–361

    CAS  PubMed  Google Scholar 

  11. Hobbs JR, Hugh-Jones K, Barrett AJ et al. (1981) Reversal of clinical features of Hurler’s disease and biochemical improvement after treatment by bone-marrow transplantation. Lancet 2:709–712

    CAS  PubMed  Google Scholar 

  12. Hurler G (1919) Über einen Typ multipler Abartungen, vorwiegend am Skelettsystem. Z Kinderheilkd 24:220–224

    Google Scholar 

  13. Johnson MA, Desai S, Hugh-Jones K et al. (1984) Magnetic resonance imaging of the brain in Hurler syndrome. Am J Neuroradiol 5:816–819

    CAS  PubMed  Google Scholar 

  14. Kakkis ED, Muenzer J, Tiller GE et al. (2001) Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med 344:182–188

    Google Scholar 

  15. Kapelushnik J, Mandel H, Varadi G et al. (2000) Fludarabine-based protocol for haploidentical peripheral blood stem cell transplantation in Hurler syndrome. J Pediatr Hematol Oncol 22:433–436

    Article  CAS  PubMed  Google Scholar 

  16. Koc ON, Day J, Nieder M et al. (2002) Allogenetic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant 30:215–222

    Article  CAS  PubMed  Google Scholar 

  17. Kremens B, Basu O, Peceny R et al. (2002) Allogeneic CD34+-selected peripheral stem cell transplantation from parental donors in children with non-malignant diseases. Bone Marrow Transplant 29:9–13

    Article  Google Scholar 

  18. Krivit W, Sung JH, Lockmann LA et al. (1995) Bone marrow transplantation for treatment of lysosomal and peroxisomal storage diseases: focus on central nervous system reconstitution. In: Rich RR, Fleisher TA, Schwartz BD et al. (eds) Principles of clinical immunology, vol 2. Mosby, St. Louis, pp 1852–1864

  19. Krivit W, Aubourg P, Shapiro E et al. (1999) Bone marrow transplantation for globoid cell leukodystrophy, adrenoleukodystrophy, metachromatic leukodystrophy, and Hurler syndrome. Curr Opin Hematol 6:377–382

    Article  CAS  PubMed  Google Scholar 

  20. Peters C, Shapiro EG, Krivit W (1998) Neuropsychological development in children with Hurler syndrome following hematopoietic stem cell transplantation. Pediatr Transplant 2:250–253

    CAS  PubMed  Google Scholar 

  21. Peters C, Balthazor M, Shapiro EG et al. (1996) Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 87:4894–4902

    CAS  PubMed  Google Scholar 

  22. Peters C, Shapiro EG, Anderson J et al. (1998) Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. Blood 91:2601–2608

    CAS  PubMed  Google Scholar 

  23. Phipps S, Mulhern R (1997) Developmental outcome of unrelated donor bone marrow transplantation in children with Hurler syndrome. Blood 89:732–734

    CAS  Google Scholar 

  24. Reisner Y, Martelli MF (2000) Transplantation tolerance induced by “mega dose” CD34+ cell transplants. Exp Hematol 28:119–127

    CAS  PubMed  Google Scholar 

  25. Russell C, Hendson G, Jevon G et al. (1998) Murine MPS I: insights into the pathogenesis of Hurler syndrome. Clin Genet 53:349–361

    CAS  PubMed  Google Scholar 

  26. Scott HS, Bunge S, Gal A et al. (1995) Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications. Hum Mutat 6:288–302

    CAS  PubMed  Google Scholar 

  27. Schmidt J, Fleissner S, Heimann-Weitschat I et al. (1994) Effect of corticosteroids, cyclosporin A, and methotrexate on cytokine release from monocytes and T-cell subsets. Immunopharmacology 27:173–179

    Article  CAS  PubMed  Google Scholar 

  28. Seto T, Kono K, Morimoto K et al. (2001) Brain magnetic resonance imaging in 23 patients with mucopolysaccharidoses and the effect of bone marrow transplantation. Ann Neurol 50:79–92

    Article  CAS  PubMed  Google Scholar 

  29. Shull RM, Kakkis ED, McEntee MF et al. (1994) Enzyme replacement in a canine model of Hurler syndrome. Proc Natl Acad Sci USA 91:12937–12941

    CAS  PubMed  Google Scholar 

  30. Vellodi A, Young EP, Cooper A et al. (1997) Bone marrow transplantation for mucopolysaccharidosis type I: experience of two British centres. Arch Dis Child 76:92–99

    CAS  PubMed  Google Scholar 

  31. Wraith JE (2001) Enzyme replacement therapy in mucopolysaccharidosis type I: progress and emerging difficulties. J Inherit Metab Dis 24:245–250

    Article  CAS  PubMed  Google Scholar 

Download references

Danksagungen

Wir danken den Schwestern und Pflegern der Mildred-Scheel-Knochenmarktransplantationsstation sowie den Schwestern unserer KMT-Ambulanz der Kinderklinik für die umsichtige und liebevolle Betreuung unserer Patienten. Wir zollen den Kindern mit MPS 1H und ihren Familien unseren Respekt und danken für die gute Zusammenarbeit während ihres schwierigen Wegs.

Author information

Authors and Affiliations

  1. Pädiatrische Hämatologie und Onkologie, Kinderklinik, Medizinische Hochschule, Hannover

    L. Grigull, A. Beilken, A. Sander, M. Schrappe, K. Welte & K. W. Sykora

  2. Pädiatrische Nieren- und Stoffwechselerkrankungen, Kinderklinik, Medizinische Hochschule, Hannover

    T. Lücke & A. Das

  3. Abteilung für Neuroradiologie, Kinderklinik, Medizinische Hochschule, Hannover

    H. P. Burmeister

  4. Abteilung für Pädiatrische Hämatologie und Onkologie, Kinderklinik, Medizinische Hochschule, Carl-Neuberg-Straße 1, 30623, Hannover

    L. Grigull

Authors
  1. L. Grigull
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Beilken
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. Lücke
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Sander
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Schrappe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. K. Welte
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. H. P. Burmeister
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K. W. Sykora
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Grigull.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Grigull, L., Beilken, A., Lücke, T. et al. Blutstammzelltransplantation bei Mukopolysaccharidose Typ 1H (Morbus Hurler) . Monatsschr Kinderheilkd 154, 49–56 (2006). https://doi.org/10.1007/s00112-004-0965-5

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00112-004-0965-5

Schlüsselwörter

Keywords

Search

Navigation