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.

  • Letter to the Editor
  • Published:

Hematopoietic stem cell transplantation for X-linked thrombocytopenia from a mild symptomatic carrier

Bone Marrow Transplantation volume 45, pages 607–609 (2010)Cite this article

The prognosis of classic Wiskott–Aldrich syndrome (WAS) with complete lack of WAS protein (WASP) expression in the absence of hematopoietic stem cell transplantation (HSCT) is poor,1, 2 whereas WASP-positive patients with the X-linked thrombocytopenia (XLT) phenotype, which is characterized by thrombocytopenia and small platelets, also have a poor long-term outcome without HSCT.3 If there is a suitable donor, HSCT is the treatment of choice for WASP-positive patients with XLT because of their high frequency of complications, including intracranial hemorrhage, autoimmune diseases and IgA nephropathy.3 Two-thirds of WASP-positive patients with splice-site mutations exhibit XLT and show the highest incidence of lymphomas, particularly for intron 6 splice-site mutations.4

We reported earlier several members of a single family diagnosed with XLT.5 Briefly, the present patient was a 9-year-old boy with a history of severe cranial hematoma at birth and purpura at the age of 2 months. He had no history of eczema, severe infection or autoimmune disease. Platelet count was 19 × 109/l with small platelets (mean platelet volume [MPV]: 4.8 fl) at age 9 years. Direct sequencing of the WASP gene revealed a splice-site G-to-A mutation at position +5 in intron 6. WASP expression levels in the patient were one-third those in the normal control, and the mother was a heterozygous carrier of the same mutation. His sister was diagnosed as a heterozygous symptomatic carrier of XLT at age 6 years, and her maternally derived X-chromosome was randomly inactivated.5 Her platelet counts increased gradually from 39 × 109/l with low MPV at diagnosis to 80 × 109/l with normal MPV at age 15 years, which suggested a proliferation/survival advantage in cells with active chromosomes bearing normal WASP or spontaneous in vivo reversion of the WASP mutation would develop.6

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
Figure 2

References

  1. Kobayashi R, Ariga T, Nonoyama S, Kanegane H, Tsuchiya S, Morio T et al. Outcome in patients with Wiskott-Aldrich syndrome following stem cell transplantation: an analysis of 57 patients in Japan. Br J Haematol 2006; 135: 362–366.

    Article  PubMed  Google Scholar 

  2. Ozsahin H, Cavazzana-Calvo M, Notarangelo LD, Schulz A, Thrasher AJ, Mazzolari E et al. Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for Blood and Marrow Transplantation. Blood 2008; 111: 439–445.

    Article  CAS  Google Scholar 

  3. Imai K, Morio T, Zhu Y, Jin Y, Itoh S, Kajiwara M et al. Clinical course of patients with WASP gene mutations. Blood 2004; 103: 456–464.

    Article  CAS  PubMed  Google Scholar 

  4. Shcherbina A, Candotti F, Rosen FS, Remold-O'Donnell E . High incidence of lymphomas in a subgroup of Wiskott-Aldrich syndrome patients. Br J Haematol 2003; 121: 529–530.

    Article  PubMed  Google Scholar 

  5. Inoue H, Kurosawa H, Nonoyama S, Imai K, Kumazaki H, Matsunaga T et al. X-linked thrombocytopenia in a girl. Br J Haematol 2002; 118: 1163–1165.

    Article  CAS  PubMed  Google Scholar 

  6. Ariga T, Kondoh T, Yamaguchi K, Yamada M, Sasaki S, Nelson DL et al. Spontaneous in vivo reversion of an inherited mutation in the Wiskott-Aldrich syndrome. J Immunol 2001; 166: 5245–5249.

    Article  CAS  PubMed  Google Scholar 

  7. Kawai S, Minegishi M, Ohashi Y, Sasahara Y, Kumaki S, Konno T et al. Flow cytometric determination of intracytoplasmic Wiskott-Aldrich syndrome protein in peripheral blood lymphocyte subpopulations. J Immunol Methods 2002; 260: 195–205.

    Article  CAS  PubMed  Google Scholar 

  8. Yamada M, Ohtsu M, Kobayashi I, Kawamura N, Kobayashi K, Ariga T et al. Flow cytometric analysis of Wiskott-Aldrich syndrome (WAS) protein in lymphocytes from WAS patients and their familial carriers. Blood 1999; 93: 756–757.

    CAS  PubMed  Google Scholar 

  9. Kubota T, Nonoyama S, Tonoki H, Masuno M, Imaizumi K, Kojima M et al. A new assay for the analysis of X-chromosome inactivation based on methylation-specific PCR. Hum Genet 1999; 104: 49–55.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Dokkyo Medical University School of Medicine, Tochigi, Japan

    M Okuya, H Kurosawa, S Hagisawa, Y Sato, T Matsushita, K Fukushima, K Sugita & O Arisaka

  2. Department of Epigenetic Medicine, University of Yamanashi, Faculty of Medicine, Yamanashi, Japan

    T Kubota, K Endoh & A Ogiwara

  3. Department of Pediatrics, National Defence Medical College, Saitama, Japan

    S Nonoyama

  4. Division of Control and Treatment on Infectious Disease, Chiba University Hospital, Chiba, Japan

    T Sato

Authors
  1. M Okuya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H Kurosawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Kubota
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K Endoh
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Ogiwara
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Nonoyama
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S Hagisawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Y Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. T Matsushita
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. K Fukushima
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. K Sugita
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. T Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. O Arisaka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H Kurosawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Okuya, M., Kurosawa, H., Kubota, T. et al. Hematopoietic stem cell transplantation for X-linked thrombocytopenia from a mild symptomatic carrier. Bone Marrow Transplant 45, 607–609 (2010). https://doi.org/10.1038/bmt.2009.200

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2009.200

Search

Advanced search

Quick links