Peripheral neuropathy in metachromatic leukodystrophy: Current status and future perspective

Shanice Beerepoot, Stefan Nierkens, Jaap Jan Boelens, Caroline Lindemans, Marianna Bugiani, Nicole I. Wolf

Research output: Contribution to journalReview articlepeer-review

49 Citations (Scopus)


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.

Original languageEnglish
Article number240
JournalOrphanet Journal of Rare Diseases
Issue number1
Publication statusPublished - 4 Nov 2019
Externally publishedYes


  • ARSA gene mutation
  • Demyelinating
  • Leukodystrophy
  • Lysosomal storage disorder
  • Metachromatic leukodystrophy
  • Neuropathy


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