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Clinical Neurology · Child Neurology

Leukodystrophies

Leukodystrophies and related white-matter disorders — inheritance, enzyme defect, clinical picture, and MRI pattern.

DiseaseInheritanceEnzyme / defectClinical pictureMRI
Adrenoleukodystrophy (peroxisomal)XL-R (ABCD gene)Failure of peroxisomal β-oxidation of VLCFA3 phenotypes:
  • Childhood cerebral adrenoleukodystrophy
  • Adrenomyeloneuropathy
  • Addison disease
  • Posterior
  • Spares U-fibers
  • 3 zones of different intensities on T2 (inner hyper, middle iso, outer hypo)
Zellweger (cerebrohepatorenal; peroxisomal)AR (PEX1)Absence of peroxisomes
  • Facies: high forehead, midface hypoplasia
  • Hepatomegaly, renal cysts
  • Diffuse hypomyelination involving U-fibers
  • Gyral abnormalities (frontal microgyria, occipital pachygyria)
Metachromatic leukodystrophy (lysosomal)AR (ARSA)Arylsulfatase A
  • Late infantile: gait abnormality, muscle rigidity, loss of vision, developmental delay
  • Juvenile: slower course
  • Adult: dementia, psychiatric features
  • Periventricular
  • Spares U-fibers → "butterfly pattern"
Krabbe (globoid cell; lysosomal)AR (GALC)GalactocerebrosidasePeripheral neuropathy, developmental delay, optic atrophy, globoid cells
  • CT: hyperdense thalami
  • MRI: periventricular
Fabry (lysosomal)XL-Rα-galactosidasePosterior-circulation strokes, peripheral neuropathy of hands/feet, angiokeratomas, cardiovascular diseasePulvinar hyperintensity
Canavan (spongiform degeneration of white matter; amino-acid)ARAspartoacylaseMacrocephaly, severe mental deficits, blindness
  • Macrocephaly
  • Diffuse hypomyelination involving U-fibers
  • Increased NAA on MRS
Alexander (fibrinoid)GFAP gene
  • Macrocephaly, severe mental deficits
  • Rosenthal fibers on pathology
  • Macrocephaly
  • Frontal predominance

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