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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

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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

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  1. M Okuya
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  2. H Kurosawa
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Correspondence to H Kurosawa.

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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

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