title: Late onset white matter disease in peroxisome biogenesis disorder.
abstract: OBJECTIVE
  To report late onset cerebral white matter disease as a distinctive phenotype in peroxisome biogenesis disorder (PBD).
  
  
  BACKGROUND
  There is phenotypic and genetic overlap among the PBD known as Zellweger syndrome (ZS), infantile Refsum disease (IRD), and neonatal adrenoleukodystrophy (NALD). Distinctive external features are variable among these three disorders, and neurologic deficit has its onset at birth or in infancy. In a structured follow-up cohort of 25 patients with PBD, not including ZS, three patients had an unusual pattern of cerebral white matter disease with onset past the age of 1, not conforming to any of the classic PBD phenotypes.
  
  
  METHODS
  Clinical phenotyping and follow-up, peroxisomal biochemical determinations in body fluids and fibroblasts, identification of affected PEX gene by genetic complementation in fibroblasts, and MRI studies.
  
  
  RESULTS
  Two unrelated patients with PBD without distinctive external features had normal neurodevelopmental milestones during their first year, followed by rapid deterioration including severe hypotonic pareses, seizures, retinopathy, and deafness. A third patient initially diagnosed with IRD developed cerebral white matter degeneration in the third year of life, complicating the original diagnosis. MRI in all three patients showed cerebral demyelination with sparing of subcortical fibers and pronounced central cerebellar demyelination.
  
  
  CONCLUSIONS
  Late-onset cerebral white matter disease may occur in PBD, either following IRD or following normal early development and in the absence of distinctive external features. Peroxisome biogenesis disorder should be included in the differential diagnosis of post-infantile onset of cerebral white matter disease
authors.affiliation: Department of Pediatrics, Emma Children's Hospital/AMC, Amsterdam, The Netherlands. p.g.barth@amc.uva.nl
authors.forename: P G
authors.initials: PG
authors.lastname: Barth
authors.forename: J
authors.initials: J
authors.lastname: Gootjes
authors.forename: H
authors.initials: H
authors.lastname: Bode
authors.forename: P
authors.initials: P
authors.lastname: Vreken
authors.forename: C B
authors.initials: CB
authors.lastname: Majoie
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
mesh_terms: D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D005500:Follow-Up Studies; D005816:Genetic Complementation Test; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging; D008297:Male; D009460:Neurologic Examination; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; D018901:Peroxisomal Disorders / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D015211:Zellweger Syndrome / Q000175:diagnosis / Q000235:genetics*
chemical_list: D011506:Proteins; D053402:PHEX Phosphate Regulating Neutral Endopeptidase; C506231:PHEX protein, human