title: Late-onset Zellweger spectrum disorder caused by PEX6 mutations mimicking X-linked adrenoleukodystrophy.
abstract: BACKGROUND
  Zellweger spectrum disorder is an autosomal recessively inherited multisystem disorder caused by one of the 13 different PEX gene defects resulting in defective peroxisomal assembly and multiple peroxisomal enzyme deficiencies. We report a new patient with late-onset Zellweger spectrum disorder mimicking X-linked adrenoleukodystrophy.
  
  
  METHODS
  This 8.5-year-old boy with normal development until 6.5 years of age presented with bilateral sensorineural hearing loss during a school hearing test. He then developed acute-onset diplopia, clumsiness, and cognitive dysfunction at age 7 years. Magnetic resonance imaging of the brain revealed symmetric leukodystrophy, although without gadolinium enhancement. Elevated plasma very long chain fatty acid levels were suggestive of X-linked adrenoleukodystrophy, but his ABCD1 gene had normal coding sequence and dosage. Additional studies of cultured skin fibroblasts were consistent with Zellweger spectrum disorder. Molecular testing identified disease-causing compound heterozygous mutations in the PEX6 gene supporting the Zellweger spectrum disorder diagnosis in this patient.
  
  
  CONCLUSIONS
  We describe a new patient with late-onset Zellweger spectrum disorder caused by PEX6 mutations who presented with an acute neurodegenerative disease course mimicking X-linked adrenoleukodystrophy. This finding provides an additional reason that molecular confirmation is important for the genetic counseling and management of patients with a clinical and biochemical diagnosis of X-linked adrenoleukodystrophy.
authors: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Christel
authors: C
authors: Tran
authors: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Stacy
authors: S
authors: Hewson
authors: Institute of Genetic Medicine and Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors: Steven J
authors: SJ
authors: Steinberg
authors: Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada; Genetics & Genome Biology Program, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: saadet.mahmutoglu@sickkids.ca.
authors: Saadet
authors: S
authors: Mercimek-Mahmutoglu
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000326:Adrenoleukodystrophy / Q000175:diagnosis; D017668:Age of Onset; D002648:Child; D003937:Diagnosis, Differential; D006801:Humans; D008297:Male; D009154:Mutation; D015211:Zellweger Syndrome / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D000251:Adenosine Triphosphatases; D000074183:ATPases Associated with Diverse Cellular Activities; C490759:PEX6 protein, human
keywords: PEX6 gene; X-linked adrenoleukodystrophy; Zellweger spectrum disorder; late onset; peroxisome biogenesis disorder