Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective

Area of Science:

• Neuroscience
• Genetics
• Metabolic Disorders

Background:

• Metachromatic leukodystrophy (MLD) is an autosomal recessive disorder due to arylsulfatase A deficiency.
• Sulfatide accumulation leads to central and peripheral nervous system demyelination, causing severe neurological symptoms and premature death.

Purpose of the Study:

• To review clinical aspects, pathology, mutations, and treatments for MLD.
• To emphasize the impact and management of peripheral neuropathy in MLD patients.

Main Methods:

• Literature review of MLD focusing on peripheral neuropathy.
• Analysis of current treatment outcomes, including hematopoietic stem cell transplantation (HCT).

Main Results:

• HCT improves outcomes for juvenile/adult MLD but shows limited efficacy for peripheral neuropathy.
• Peripheral neuropathy contributes significantly to MLD morbidity, with reasons for post-HCT progression unclear.
• Neuroinflammation may play a role in MLD peripheral neuropathy.

Conclusions:

• Future MLD therapies require greater focus on managing peripheral neuropathy.
• Additional research is crucial to optimize care strategies for MLD peripheral neuropathy.