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Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective

Metachromatic leukodystrophy (MLD) is an autosomal recessively inherited metabolic disease characterized by deficient activity of the lysosomal enzyme arylsulfatase A. Its deficiency results in accumulation of sulfatides in neural and visceral tissues, and causes demyelination of the central and per...

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Autores principales: Beerepoot, Shanice, Nierkens, Stefan, Boelens, Jaap Jan, Lindemans, Caroline, Bugiani, Marianna, Wolf, Nicole I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829806/
https://www.ncbi.nlm.nih.gov/pubmed/31684987
http://dx.doi.org/10.1186/s13023-019-1220-4
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author Beerepoot, Shanice
Nierkens, Stefan
Boelens, Jaap Jan
Lindemans, Caroline
Bugiani, Marianna
Wolf, Nicole I.
author_facet Beerepoot, Shanice
Nierkens, Stefan
Boelens, Jaap Jan
Lindemans, Caroline
Bugiani, Marianna
Wolf, Nicole I.
author_sort Beerepoot, Shanice
collection PubMed
description Metachromatic leukodystrophy (MLD) is an autosomal recessively inherited metabolic disease characterized by deficient activity of the lysosomal enzyme arylsulfatase A. Its deficiency results in accumulation of sulfatides in neural and visceral tissues, and causes demyelination of the central and peripheral nervous system. This leads to a broad range of neurological symptoms and eventually premature death. In asymptomatic patients with juvenile and adult MLD, treatment with allogeneic hematopoietic stem cell transplantation (HCT) provides a symptomatic and survival benefit. However, this treatment mainly impacts brain white matter, whereas the peripheral neuropathy shows no or only limited response. Data about the impact of peripheral neuropathy in MLD patients are currently lacking, although in our experience peripheral neuropathy causes significant morbidity due to neuropathic pain, foot deformities and neurogenic bladder disturbances. Besides, the reasons for residual and often progressive peripheral neuropathy after HCT are not fully understood. Preliminary studies suggest that peripheral neuropathy might respond better to gene therapy due to higher enzyme levels achieved than with HCT. However, histopathological and clinical findings also suggest a role of neuroinflammation in the pathology of peripheral neuropathy in MLD. In this literature review, we discuss clinical aspects, pathological findings, distribution of mutations, and treatment approaches in MLD with particular emphasis on peripheral neuropathy. We believe that future therapies need more emphasis on the management of peripheral neuropathy, and additional research is needed to optimize care strategies.
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spelling pubmed-68298062019-11-07 Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective Beerepoot, Shanice Nierkens, Stefan Boelens, Jaap Jan Lindemans, Caroline Bugiani, Marianna Wolf, Nicole I. Orphanet J Rare Dis Review Metachromatic leukodystrophy (MLD) is an autosomal recessively inherited metabolic disease characterized by deficient activity of the lysosomal enzyme arylsulfatase A. Its deficiency results in accumulation of sulfatides in neural and visceral tissues, and causes demyelination of the central and peripheral nervous system. This leads to a broad range of neurological symptoms and eventually premature death. In asymptomatic patients with juvenile and adult MLD, treatment with allogeneic hematopoietic stem cell transplantation (HCT) provides a symptomatic and survival benefit. However, this treatment mainly impacts brain white matter, whereas the peripheral neuropathy shows no or only limited response. Data about the impact of peripheral neuropathy in MLD patients are currently lacking, although in our experience peripheral neuropathy causes significant morbidity due to neuropathic pain, foot deformities and neurogenic bladder disturbances. Besides, the reasons for residual and often progressive peripheral neuropathy after HCT are not fully understood. Preliminary studies suggest that peripheral neuropathy might respond better to gene therapy due to higher enzyme levels achieved than with HCT. However, histopathological and clinical findings also suggest a role of neuroinflammation in the pathology of peripheral neuropathy in MLD. In this literature review, we discuss clinical aspects, pathological findings, distribution of mutations, and treatment approaches in MLD with particular emphasis on peripheral neuropathy. We believe that future therapies need more emphasis on the management of peripheral neuropathy, and additional research is needed to optimize care strategies. BioMed Central 2019-11-04 /pmc/articles/PMC6829806/ /pubmed/31684987 http://dx.doi.org/10.1186/s13023-019-1220-4 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Review
Beerepoot, Shanice
Nierkens, Stefan
Boelens, Jaap Jan
Lindemans, Caroline
Bugiani, Marianna
Wolf, Nicole I.
Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective
title Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective
title_full Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective
title_fullStr Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective
title_full_unstemmed Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective
title_short Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective
title_sort peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829806/
https://www.ncbi.nlm.nih.gov/pubmed/31684987
http://dx.doi.org/10.1186/s13023-019-1220-4
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