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Updated: May 3 2019

Metachromic Leukodystrophy

Images
https://upload.medbullets.com/topic/120311/images/mld.jpg
https://upload.medbullets.com/topic/120311/images/metachromic_leukodystrophy.jpg
https://upload.medbullets.com/topic/120311/images/01222017llstep1lysosomalstoragedisrdero-01-01.jpg
  • Snapshot
    • A 12-year-old boy presents to his pediatrician due to troubles with his gait and increasing difficulty in school. His parents also report him having a seizure episode, requiring stabilization at a local hospital. Neurological examination is notable for ataxia and decreased pain, temperature, and vibration sense in his bilateral lower extremities. He also has bilateral upgoing toes. An MRI brain demonstrates bilateral and symmetric white matter changes in the periventricular region. There is reduced arylsulfatase activity in his leukocytes.
  • Introduction
    • Definition
      • autosomal recessive lysosomal storage disorder that leads to progressive demyelination of both central and peripheral nerves
  • Epidemiology
    • Incidence
      • rare
  • Pathogenesis
    • Arylsulfatase A deficiency (secondary to a gene mutation in most cases) leads to cerebroside sulfate accumulation
      • this damages Schwann cells and oligodendrocytes, leading to central and peripheral nerve demyelination
  • Presentation
    • Symptoms/physical exam
      • late infantile onset (6 months - 2 years)
        • regression of motor skills
        • gait difficulties
        • optic atrophy
        • seizures
      • juvenile onset (3-16 years)
        • intellectual impairment and behavioral difficulties
        • gait disturbances
        • peripheral neuropathy
      • adult (> 16 years)
        • dementia
        • psychiatric disease
        • neuropathy
  • Imaging
    • MRI brain
      • indication
        • performed with patients with progressive neurological deficits
      • findings
        • symmetrical bilateral periventricular hyperintensities
          • leads to a "butterfly pattern"
        • atrophy in progressive disease
  • Studies
    • Serum
      • reduced arylsufatase A gene activity in leukocytes or cultured skin fibroblasts
    • Urine
      • increased urine sulfatides
  • Differential
    • Krabbe disease
      • differentiating factor
        • caused by a galactocerebrosidase deficiency
    • Tay-sachs disease
      • differentiating factor
        • caused by a hexosaminidase A deficiency
  • Treatment
    • No effective treatment
  • Complications
    • Seizures
    • Learning disabilities
    • Gait difficulties
    • Gallbladder complications
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