The University of Southampton
University of Southampton Institutional Repository

Hematopoietic stem cell transplantation for late-onset Metachromatic Leukodystrophy

Hematopoietic stem cell transplantation for late-onset Metachromatic Leukodystrophy
Hematopoietic stem cell transplantation for late-onset Metachromatic Leukodystrophy
Haematopoietic stem cell transplantation has an unproven role in the management of late-onset metachromatic leukodystrophy: theoretically justified through the engraftment of enzyme-replete haematopoietic progenitors and restoration of capacity for sulphatide catabolism in neural tissue through enzyme recapture, the long-term outcome is unknown. The rarity of the psycho-cognitive variant and slow progression of late-onset disease impairs evaluation of treatment. We report detailed clinical and neuropsychological assessments after haematopoietic stem-cell transplantation in a patient with a late-onset psycho-cognitive form of metachromatic leukodystrophy. Cognitive decline, indistinguishable from the natural course of the disease, was serially documented over 11 years despite complete donor chimaerism and correction of leukocyte arylsulphatase A to wild type values; subtle motor deterioration was similarly noted and progressive cerebral volume loss was evident upon magnetic resonance imaging. Sensory nerve conduction deteriorated 17 months post-transplantation with apparent stabilisation at 11-year review. Haematopoietic stem-cell transplantation was ineffective for this rare attenuated variant of metachromatic leukodystrophy. In the few patients identified pre-symptomatically or with early-phase disease, clear recommendations are lacking; when transplantation is considered, umbilical cord blood grafts from enzyme-replete donors with adjunctive mesenchymal stem cell infusions from the same source may be preferable. Improved outcomes will depend on enhanced awareness and early diagnosis of the disease, so that promising interventions such as genetically modified, autologous stem cell transplantation have the best opportunity of success.
0141-8955
Smith, Nicholas J.
d76ec965-3830-45f3-9213-8ee6dedf86f3
Marcus, Robert
a16601ff-650d-473e-a0ff-81558e16cef5
Sahakian, Barbara
d180cbfe-a554-4983-90d5-c9a578053637
Kapur, Narinder
9ea5d758-bba6-4bc9-be6b-b056c0c83d9d
Cox, Timothy M.
b8dc4f25-e234-4c01-b156-faee786d558e
Smith, Nicholas J.
d76ec965-3830-45f3-9213-8ee6dedf86f3
Marcus, Robert
a16601ff-650d-473e-a0ff-81558e16cef5
Sahakian, Barbara
d180cbfe-a554-4983-90d5-c9a578053637
Kapur, Narinder
9ea5d758-bba6-4bc9-be6b-b056c0c83d9d
Cox, Timothy M.
b8dc4f25-e234-4c01-b156-faee786d558e

Smith, Nicholas J., Marcus, Robert, Sahakian, Barbara, Kapur, Narinder and Cox, Timothy M. (2011) Hematopoietic stem cell transplantation for late-onset Metachromatic Leukodystrophy. Journal of Inherited Metabolic Disease. (doi:10.1007/s10545-010-9240-1).

Record type: Article

Abstract

Haematopoietic stem cell transplantation has an unproven role in the management of late-onset metachromatic leukodystrophy: theoretically justified through the engraftment of enzyme-replete haematopoietic progenitors and restoration of capacity for sulphatide catabolism in neural tissue through enzyme recapture, the long-term outcome is unknown. The rarity of the psycho-cognitive variant and slow progression of late-onset disease impairs evaluation of treatment. We report detailed clinical and neuropsychological assessments after haematopoietic stem-cell transplantation in a patient with a late-onset psycho-cognitive form of metachromatic leukodystrophy. Cognitive decline, indistinguishable from the natural course of the disease, was serially documented over 11 years despite complete donor chimaerism and correction of leukocyte arylsulphatase A to wild type values; subtle motor deterioration was similarly noted and progressive cerebral volume loss was evident upon magnetic resonance imaging. Sensory nerve conduction deteriorated 17 months post-transplantation with apparent stabilisation at 11-year review. Haematopoietic stem-cell transplantation was ineffective for this rare attenuated variant of metachromatic leukodystrophy. In the few patients identified pre-symptomatically or with early-phase disease, clear recommendations are lacking; when transplantation is considered, umbilical cord blood grafts from enzyme-replete donors with adjunctive mesenchymal stem cell infusions from the same source may be preferable. Improved outcomes will depend on enhanced awareness and early diagnosis of the disease, so that promising interventions such as genetically modified, autologous stem cell transplantation have the best opportunity of success.

Full text not available from this repository.

More information

Published date: 5 April 2011

Identifiers

Local EPrints ID: 183199
URI: http://eprints.soton.ac.uk/id/eprint/183199
ISSN: 0141-8955
PURE UUID: 9b5672ff-92b3-4e52-9f60-dd3a56045a74

Catalogue record

Date deposited: 28 Apr 2011 15:34
Last modified: 16 Jul 2019 23:40

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×