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Sustained neurological improvement following reduced-intensity conditioning allogeneic haematopoietic stem cell transplantation for late-onset Krabbe disease

Bone Marrow Transplantation volume 41, pages 831–832 (2008)Cite this article

Krabbe disease, or globoid cell leukodystrophy, is an autosomal recessive disease caused by a deficiency of the lysosomal enzyme galactocerebrosidase (GALC).1 Galactocerebroside and its toxic by-product psychosine accumulate in multinucleated macrophages (globoid cells) causing a progressive loss of myelin and secondary neuronal loss in the central and peripheral nervous system. Typically, an onset in infancy leads to delay in achieving motor milestones by 9 months followed by seizures, spasticity, blindness and progressive cognitive decline until death by the age of 2 years. Late-onset Krabbe disease occurs in early childhood or adulthood, and usually presents with a progressive spasticity, ataxia and subtle cognitive impairment, leading to death in early adulthood.2

Standard myeloablative allogeneic haematopoietic stem cell transplantation (HSCT) has been demonstrated to correct the metabolic defect3 in Krabbe disease, albeit with significant associated morbidity. Donor-derived monocyte–macrophages with normal GALC repopulate the glial cells of the nervous system, providing a microenvironment with normal metabolic activity. Within the last 5 years, reduced-intensity HSCT has proven to be safe and efficacious in a variety of haematological and non-haematological malignancies with significantly reduced toxicity.4 Here, we report a successful case of reduced-intensity transplantation performed for late-onset globoid cell leukodystrophy.

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Authors and Affiliations

  1. Department of Haematological Medicine, King's College London, Kings College Hospital NHS Foundation Trust, London, UK

    Z Y Lim, A Y L Ho, A Pagliuca & G J Mufti

  2. Department of Psychology, Institute of Psychology, London, UK

    S Abrahams

  3. King's College London, SAS Genetic Enzyme Laboratory, Guy's Hospital, London, UK

    A Fensom

  4. Department of Haematological Medicine, Medway Maritime Hospital, Kent, UK

    M Aldouri

  5. Department of Neurology, King's College London, Institute of Psychiatry, Kings College Hospital NHS Foundation Trust, London, UK

    C Shaw

Authors
  1. Z Y Lim
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  2. A Y L Ho
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  3. S Abrahams
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  4. A Fensom
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  5. M Aldouri
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  6. A Pagliuca
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  7. C Shaw
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  8. G J Mufti
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Correspondence to G J Mufti.

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Lim, Z., Ho, A., Abrahams, S. et al. Sustained neurological improvement following reduced-intensity conditioning allogeneic haematopoietic stem cell transplantation for late-onset Krabbe disease. Bone Marrow Transplant 41, 831–832 (2008). https://doi.org/10.1038/sj.bmt.1705984

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