Neuroimaging of peroxisome biogenesis disorders (Zellweger spectrum) with prolonged survival

Neurology. 2004 Feb 10;62(3):439-44. doi: 10.1212/01.wnl.0000106943.40848.03.

Abstract

Objective: To define neuroimaging characteristics of peroxisome biogenesis disorders (PBD) with prolonged survival belonging to the Zellweger spectrum (ZeS).

Methods: The authors studied MR images of 25 patients surviving the first year. Neuroimages were compared to neurologic profiles, PBD-ZeS specific compound developmental scores, and two common PEX1 mutations.

Results: Three groups are defined based on normal findings, developmental anomalies, and regressive changes. Regressive changes consisting of leukoencephalopathy were identified in patients who had either stable clinical course or progressive deterioration. Concomitant neocortical atrophy was encountered in a minority. Leukoencephalopathy with stable clinical course represents the largest subgroup (48%). The authors found the central cerebellar white matter a focus for early changes in both asymptomatic and symptomatic leukoencephalopathy. A relationship between white matter involvement in clinically stable leukoencephalopathy and degree of developmental failure could not be established. The common homozygous PEX1 G843D mutation is represented in the three main outcome groups. This result points to variable phenotypic expression of the most common PEX1 mutation.

Conclusions: MR findings in ZeS patients surviving the first year differ from Zellweger syndrome in predominance of regressive over developmental changes. Distribution pattern suggests identical pathomechanisms for symptomatic and asymptomatic leukoencephalopathy.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Adolescent
  • Adult
  • Amino Acid Substitution
  • Atrophy
  • Cerebral Ventricles / pathology*
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • Humans
  • Infant
  • Male
  • Membrane Proteins / genetics
  • Mutation, Missense
  • Myelin Sheath / pathology
  • Neocortex / pathology*
  • Phenotype
  • Survival Analysis
  • Zellweger Syndrome / classification
  • Zellweger Syndrome / genetics
  • Zellweger Syndrome / mortality
  • Zellweger Syndrome / pathology*

Substances

  • Membrane Proteins
  • ATPases Associated with Diverse Cellular Activities
  • PEX1 protein, human