Long-term outcome of patients with X-linked adrenoleukodystrophy: A retrospective cohort study

Christel Tran; Jaina Patel; Hewson Stacy; Eva G Mamak; Hanna Faghfoury; Julian Raiman; Joe T R Clarke; Susan Blaser; Saadet Mercimek-Mahmutoglu

doi:10.1016/j.ejpn.2017.02.006

Long-term outcome of patients with X-linked adrenoleukodystrophy: A retrospective cohort study

Eur J Paediatr Neurol. 2017 Jul;21(4):600-609. doi: 10.1016/j.ejpn.2017.02.006. Epub 2017 Feb 21.

Authors

Christel Tran¹, Jaina Patel², Hewson Stacy², Eva G Mamak³, Hanna Faghfoury⁴, Julian Raiman², Joe T R Clarke², Susan Blaser⁵, Saadet Mercimek-Mahmutoglu⁶

Affiliations

¹ 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.
² Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
³ Department of Psychology, The Hospital for Sick Children, Canada.
⁴ The Fred A Litwin and Family Centre in Genetic Medicine, University Health Network and Mount Sinai Hospital, Toronto, Canada.
⁵ Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada.
⁶ 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.

PMID: 28274546
DOI: 10.1016/j.ejpn.2017.02.006

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.

Method: 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.

Conclusion: 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.

Keywords: Addison's disease; Leukodystrophy; Very long chain fatty acids; X-linked adrenoleukodystrophy.

MeSH terms

Adrenoleukodystrophy / complications
Adrenoleukodystrophy / diagnosis*
Adrenoleukodystrophy / physiopathology
Cohort Studies
Female
Humans
Male
Retrospective Studies