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

• Published in: European journal of paediatric neurology Vol. 21; no. 4; pp. 600 - 609
• Main Authors: Tran, Christel, MD, Patel, Jaina, Stacy, Hewson, Mamak, Eva G, Faghfoury, Hanna, Raiman, Julian, Clarke, Joe TR, Blaser, Susan, Mercimek-Mahmutoglu, Saadet
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-07-2017
• Subjects: Addison's disease; Adrenoleukodystrophy - complications; Adrenoleukodystrophy - diagnosis; Adrenoleukodystrophy - physiopathology; Cohort Studies; Female; Humans; Leukodystrophy; Male; Neurology; Pediatrics; Retrospective Studies; Very long chain fatty acids; X-linked adrenoleukodystrophy; Wechsler Preschool and Primary Scale of Intelligence, Third Edition; MRI; X-linked adrenoleukodystrophy; WPPSI-III; ACTH; leukodystrophy; Adrenocorticotropin; N-acetylaspartate; MRS; Magnetic resonance spectroscopy; FSIQ; CCALD; Wechsler Intelligence Scale for Children fourth edition; VLCFA; HSCT; Wechsler Adult Intelligence Scale fourth edition; Hematopoietic stem cell transplantation; MRSS; Addison’s disease; very long chain fatty acids; AI; Visual-motor integration; Performance intelligence quotient; X-ALD; NAA; Very long chain fatty acid; Childhood cerebral X-ALD; WAIS-IV; Adrenal insufficiency; VMI; Magnetic resonance imaging; Moser-Raymond Severity Score; WISC-IV; PIQ; Full scale intelligence quotient (IQ) score; Very long chain fatty acids; Leukodystrophy; Addison's disease
• ISSN: 1090-3798; 1532-2130
• 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 1989-2012 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.