Table 2

Clinical features associated with adult onset leukodystrophies

Suggestive presenting featuresLeukodystrophy
Visual involvement
 Optic atrophyMetachromatic leukodystrophy, Krabbe disease, mitochondrial disorders, Pelizaeus–Merzbacher disease
 Cortical blindnessKrabbe disease
 Retinal degenerationKrabbe disease, mitochondrial disorders, Cockayne syndrome
 CataractsCerebrotendinous xanthomatosis, mitochondrial disorders
 Abnormal eye movements/nystagmusPelizaeus–Merzbacher disease, Pelizaeus–Merzbacher-like disease
Neurological features
 Peripheral neuropathyMetachromatic leukodystrophy (but often not seen in adult onset)
Cerebrotendinous xanthomatosis
Krabbe disease
Adult polyglucosan body disease
 Cerebellar ataxiaCerebrotendinous xanthomatosis
Alexander disease
Adult polyglucosan body disease
Vanishing white matter disease
 Psychiatric symptomsMetachromatic leukodystrophy
Vanishing white matter disease
Cerebral adrenoleukodystrophy
Hereditary diffuse leukoencephalopathy with axonal spheroids
 Pyramidal weakness/spasticityAdrenomyeloneuropathy/adrenoleukodystrophy
Krabbe disease
Cerebrotendinous xanthomatosis
Vanishing white matter disease
Adult polyglucosan body disease
Hereditary diffuse leukoencephalopathy with axonal spheroids
 Bulbar dysfunction and palatal myoclonusAdult onset Alexander disease
 Dystonic dyskinetic movement disorderGlutaricacidemia type 1
 Autonomic featuresAdult onset autosomal dominant leukodystrophy
 Migraine and strokeCADASIL
Other features
 Primary/secondary amenorrhoeaVanishing white matter disease
 Fractures following minor traumaPolycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (Nasu–Hokola disease)
 MacrocephalyAlexander disease, organic acidurias (Canavan disease, glutaricacidemia type 1, L-2-hydroxyglutaric aciduria), megalencephalic leukoencephalopathy with subcortical cysts
 Tendon xanthomaCerebrotendinous xanthomatosis
  • CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.