title: MRI as diagnostic tool in early-onset peroxisomal disorders.
abstract: OBJECTIVE
  Peroxisomal blood tests are generally considered to be conclusive. We observed several patients with a clinical and MRI phenotype suggestive of an infantile onset peroxisomal defect, but no convincing abnormalities in initial peroxisomal blood tests. Brain MRI showed typical abnormalities as observed in the neonatal adrenoleukodystrophy variant of infantile peroxisomal disorders. Our aim was to evaluate the accuracy of this MRI diagnosis with further peroxisomal testing.
  
  
  METHODS
  We searched our database of unclassified leukoencephalopathies and found 6 such patients. We collected clinical data and scored available MRIs of these patients. We performed further peroxisomal studies in fibroblasts, including immunofluorescence microscopy analysis with antibodies against catalase, a peroxisomal matrix enzyme. We performed complementation analysis and analyzed the suspected genes.
  
  
  RESULTS
  We confirmed the diagnosis of Zellweger spectrum disorder in 3 patients and D-bifunctional protein deficiency in the others. The clinical findings were within the spectrum known for these diagnoses. Sequential MRIs showed that the abnormalities started in the hilus of the dentate nucleus and superior cerebellar peduncles. Subsequently, the cerebellar white matter and brainstem tracts were affected, followed by the parieto-occipital white matter, splenium of the corpus callosum, and posterior limb of the internal capsule. Eventually, all cerebral white matter became abnormal. The thalamus was typically affected as well.
  
  
  CONCLUSIONS
  If MRI reveals abnormalities suggestive of infantile onset peroxisomal defects, negative peroxisomal blood tests do not exclude the diagnosis. Further tests in fibroblasts should be performed, most importantly immunofluorescence microscopy analysis with antibodies against catalase to stain peroxisomes.
authors.affiliation: Department of Child Neurology, VU University Medical Center, Amsterdam, the Netherlands. ms.vanderknaap@vumc.nl
authors.forename: M S
authors.initials: MS
authors.lastname: van der Knaap
authors.forename: E
authors.initials: E
authors.lastname: Wassmer
authors.forename: N I
authors.initials: NI
authors.lastname: Wolf
authors.forename: P
authors.initials: P
authors.lastname: Ferreira
authors.forename: M
authors.initials: M
authors.lastname: Topçu
authors.forename: R J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: H R
authors.initials: HR
authors.lastname: Waterham
authors.forename: S
authors.initials: S
authors.lastname: Ferdinandusse
mesh_terms: D001921:Brain / Q000473:pathology*; D001933:Brain Stem / Q000473:pathology; D002529:Cerebellar Nuclei / Q000473:pathology; D002531:Cerebellum / Q000473:pathology; D002675:Child, Preschool; D003337:Corpus Callosum / Q000473:pathology; D003937:Diagnosis, Differential; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D007231:Infant, Newborn; D020772:Internal Capsule / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D018901:Peroxisomal Disorders / Q000175:diagnosis*; D012035:Refsum Disease / Q000175:diagnosis; D012189:Retrospective Studies; D015211:Zellweger Syndrome / Q000175:diagnosis