title: Defective peroxisome biogenesis with a neuromuscular disorder resembling Werdnig-Hoffmann disease.
abstract: OBJECTIVE
  Characterization of the defect in a patient presenting a peripheral neuropathy with atypical features of distal motor involvement mimicking Werdnig-Hoffmann disease.
  
  
  METHODS
  Clinical signs included generalized hypotonia and floppiness, absence of stretch reflexes, muscle wasting, lack of head control and lingual fasciculations associated with unaffected facial muscles, and normal intellectual development.
  
  
  RESULTS
  Normal muscle histology ruled out Werdnig-Hoffmann disease. Elevated plasma concentrations of very long-chain fatty acids and bile acid intermediates combined with normal plasmalogen levels in erythrocytes suggested defective peroxisomal beta-oxidation directly demonstrated by deficient pristanic acid and partially deficient C26:0 was present oxidation in cultured fibroblasts. Severely impaired pipecolic acid oxidation in liver and phytanic acid oxidation in fibroblasts was present. On light and electron microscopy of the liver tissue, rare peroxisomal membrane ghosts and trilamellar inclusions but absence of peroxisomes was noted. Immunoblot analysis revealed absence of peroxisomal beta-oxidation enzymes in liver tissue but normal results in fibroblasts. Remarkably, expression of the peroxisomal defect in fibroblasts was indicated by the finding of mainly cytoplasmatic catalase, as in liver. Preliminary studies excluded classification of this patient within the large PEX1 complementation group.
  
  
  CONCLUSIONS
  The results suggest a novel peroxisome biogenesis disorder involving peroxisomal beta-oxidation as well as phytanic and pipecolic acid oxidation rather than an isolated defect of peroxisomal beta-oxidation. The association of a clinical picture mimicking Werdnig-Hoffmann disease with a novel peroxisomal disorder raises the question of whether investigation for peroxisomal function should be considered in every patient with an enigmatic spinal muscular atrophy-like syndrome.
authors.affiliation: Department of Pediatrics, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: M R
authors.initials: MR
authors.lastname: Baumgartner
authors.forename: N M
authors.initials: NM
authors.lastname: Verhoeven
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: F
authors.initials: F
authors.lastname: Roels
authors.forename: M
authors.initials: M
authors.lastname: Espeel
authors.forename: M
authors.initials: M
authors.lastname: Martinez
authors.forename: D
authors.initials: D
authors.lastname: Rabier
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
authors.forename: J M
authors.initials: JM
authors.lastname: Saudubray
mesh_terms: D001647:Bile Acids and Salts / Q000097:blood; D002478:Cells, Cultured; D003937:Diagnosis, Differential; D004912:Erythrocytes / Q000378:metabolism; D017809:Fatal Outcome; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007223:Infant; D007360:Intelligence; D008099:Liver / Q000378:metabolism; D008830:Microbodies / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D018482:Muscle, Skeletal / Q000473:pathology; D010875:Pipecolic Acids / Q000097:blood / Q000652:urine; D014897:Spinal Muscular Atrophies of Childhood / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology*; D015211:Zellweger Syndrome / Q000175:diagnosis* / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D001647:Bile Acids and Salts; D005230:Fatty Acids, Nonesterified; D010875:Pipecolic Acids; C031345:pipecolic acid