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Metachromatic leukodystrophy
Other Resources UpToDate PubMed

Metachromatic leukodystrophy

Contributors: Bo Hoon Lee MD, Jamie Adams MD, Richard L. Barbano MD, PhD
Other Resources UpToDate PubMed


Metachromatic leukodystrophy (MLD) is an autosomal recessive disorder caused by mutations in the ARSA gene, which encodes arylsulfatase A enzyme. Arylsulfatase A deficiency leads to impaired breakdown of sulfatides. Sulfatide accumulation in the central nervous system (CNS) leads to myelin breakdown. Sulfatides can also accumulate in the peripheral nervous system, kidneys, and gallbladder.

MLD is characterized by 3 clinical subtypes with variable age of onset and progression:
  • Late-infantile MLD is the most common and has onset before 30 months of age; it typically presents with progressive hypotonia, weakness, and dysarthria and regression of cognitive, language, and motor skills. Most children die within 5 years after onset of symptoms.
  • Juvenile MLD has onset between 30 months and 16 years of age. Initial symptoms can involve worsening school performance, personality changes, and behavioral issues. Progression of neurologic symptoms is variable. The majority of patients die before 20 years of age.
  • Adult MLD has onset after 16 years of age and has a highly variable presentation. Initial symptoms often involve declining job performance or psychiatric symptoms, often leading to initial diagnosis of mood disorders or psychosis. Neurologic symptoms include weakness, peripheral neuropathy, loss of coordination, and spasticity.


E75.25 – Metachromatic leukodystrophy

396338004 – Metachromatic leukodystrophy

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Differential Diagnosis & Pitfalls

  • Krabbe disease
  • Adrenoleukodystrophy
  • Pelizaeus-Merzbacher disease
  • Canavan disease
  • Alexander disease
  • Vanishing white matter disease
  • Gaucher disease type 2
  • Niemann-Pick disease
  • Tay-Sachs disease
  • Sandhoff disease
  • Neuronal ceroid lipofuscinoses
  • Acute demyelinating encephalomyelitis
  • Anti-N-methyl-D-aspartate receptor antibody syndrome
  • CNS infection, eg, Progressive multifocal leukoencephalopathy
  • Brain tumor, eg, Glioblastoma multiforme, CNS Lymphoma
  • Hypoxic ischemic encephalopathy
  • Toxic leukoencephalopathy, eg, chemotherapy induced
  • Attention deficit hyperactivity disorder (ADHD)
  • Dementia
  • Schizophrenia spectrum disorders
Arylsulfatase A activity may be low in many other disorders (pseudodeficiency). Urinary sulfatides should be measured as the next confirmatory step.

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Last Reviewed:06/17/2018
Last Updated:10/10/2022
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Metachromatic leukodystrophy
A medical illustration showing key findings of Metachromatic leukodystrophy : Ataxia, Gait disturbance, Nystagmus, Optic disc atrophy, Spasticity, Memory loss
Copyright © 2024 VisualDx®. All rights reserved.