Zellweger Spectrum Disorder

Main Features

  • Range of multisystemic manifestations of varying severity involving the following systems: neurologic, liver, adrenal, bone, hearing, vision
  • Disease severity associated with level of residual PEX protein function in the peroxisomes
  • AKA: Zellweger syndrome (severe) neonatal adrenoleukodystrophy (intermediate severity), infantile Refsum disease (mild) and Heimler syndrome (milder)

Eye Findings

  • Progressive retinopathy leading to blindness
    • retinitis pigmentosa
    • macular atrophy
    • extinguished ERG
    • retinal arteriolar attenuation
    • Cystoid macular edema
    • peripheral visual field loss
    • nyctalopia
    • dyschromatopsia
    • Optic nerve atrophy
    • nystagmus and poor visual acuity
  • Cataracts
  • Corneal clouding
  • Glaucoma

Other Findings

  • Severe types
    • newborn hypotonia
    • congenital malformations associated with neuronal migration deficits
      • neonatal seizures, renal cysts, bony stippling (chrondroplasia punctata), liver disease
  • Intermediate or mild subtypes
    • progressive peroxisome dysfunction with sensory loss
      • hearing and vision, ataxia, polyneuropathy, leukodystrophy,
      • liver dysfunction, adrenal insufficiency, renal oxalate stones
      • ameleogenesis imperfecta of the secondary teeth

Etiology

  • Peroxisome biogenesis disorder caused by biallelic mutations in the 13 PEX genes

Resources