title: Long-term outcome of patients with X-linked adrenoleukodystrophy: A retrospective cohort study.
abstract: BACKGROUND
  X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder associated with leukodystrophy, myeloneuropathy and adrenocortical insufficiency. We performed a retrospective cohort study to evaluate long-term outcome of patients with X-ALD.
  
  
  METHODS
  All patients with X-ALD diagnosed between 1989 and 2012 were included. Electronic patient charts were reviewed for clinical features, biochemical investigations, molecular genetic testing, neuroimaging, long-term outcome and treatment.
  
  
  RESULTS
  Forty-eight patients from 18 unrelated families were included (15 females; 33 males). Seventeen patients were symptomatic at the time of the biochemical diagnosis including 14 with neurocognitive dysfunction and 3 with Addison disease only. Thirty-one asymptomatic individuals were identified by positive family history of X-ALD. During follow-up, eight individuals developed childhood cerebral X-ALD (CCALD), one individual developed adrenomyeloneuropathy (AMN), six individuals developed Addison disease only, and five individuals remained asymptomatic. Direct sequencing of ABCD1 confirmed the genetic diagnosis in 29 individuals. Seven patients with CCALD underwent hematopoietic stem cell transplantation (HSCT). Nine patients lost the follow-up. There was no correlation between clinical severity score, Loes score and elevated degree of elevated very long chain fatty acid (VLCFA) levels in CCALD.
  
  
  CONCLUSIONS
  Our study reports forty-eight new patients with X-ALD and their long-term outcome. Only 35% of the patients presented with neurological features or Addison disease. The remaining individuals were identified due to positive family history. Close monitoring of asymptomatic males resulted in early HSCT to prevent progressive lethal neurodegenerative disease. Identification of patients with X-ALD is important to improve neurodevelopmental outcome of asymptomatic males.
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada; Division of Genetic Medicine, Center for Molecular Diseases, Lausanne University Hospital, Lausanne, Switzerland; Service of Endocrinology, Diabetes and Metabolism, Lausanne University Hospital, Lausanne, Switzerland. Electronic address: Christel.tran@chuv.ch.
authors.forename: Christel
authors.initials: C
authors.lastname: Tran
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Jaina
authors.initials: J
authors.lastname: Patel
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Hewson
authors.initials: H
authors.lastname: Stacy
authors.affiliation: Department of Psychology, The Hospital for Sick Children, Canada.
authors.forename: Eva G
authors.initials: EG
authors.lastname: Mamak
authors.affiliation: The Fred A Litwin and Family Centre in Genetic Medicine, University Health Network and Mount Sinai Hospital, Toronto, Canada.
authors.forename: Hanna
authors.initials: H
authors.lastname: Faghfoury
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Julian
authors.initials: J
authors.lastname: Raiman
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Joe T R
authors.initials: JTR
authors.lastname: Clarke
authors.affiliation: Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada.
authors.forename: Susan
authors.initials: S
authors.lastname: Blaser
authors.affiliation: Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada; Genetics and Genome Biology, Research Institute, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Saadet
authors.initials: S
authors.lastname: Mercimek-Mahmutoglu
mesh_terms: D000326:Adrenoleukodystrophy / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D012189:Retrospective Studies
keywords: Addison's disease; Leukodystrophy; Very long chain fatty acids; X-linked adrenoleukodystrophy