Biochemical Aspects of X-Linked Adrenoleukodystrophy

Authors

  • Stephan Kemp,

    1. Academic Medical Center, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Departments of Pediatrics/Emma Children's Hospital and Clinical Chemistry, Amsterdam, the Netherlands
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  • Ronald Wanders

    1. Academic Medical Center, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Departments of Pediatrics/Emma Children's Hospital and Clinical Chemistry, Amsterdam, the Netherlands
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Stephan Kemp, PhD, Academic Medical Center, University of Amsterdam, Laboratory Genetic Metabolic Diseases, Departments of Pediatrics/Emma Children's Hospital and Clinical Chemistry, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands (E-mail: s.kemp@amc.uva.nl.)

Abstract

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. The disease is characterized by the accumulation of very long-chain fatty acids (VLCFA; >C22) in plasma and tissues. X-ALD is caused by mutations in the ABCD1 gene encoding ALDP, an adenosine triphosphate (ATP)-binding-cassette (ABC) transporter located in the peroxisomal membrane. In this paper, we describe the current knowledge on the function of ALDP, its role in peroxisomal VLCFA beta-oxidation and the consequences of a defect in ALDP on VLCFA metabolism. Furthermore, we pay special attention to the role of the VLCFA elongation system in VLCFA homeostasis, with elongation of very long-chain fatty acids like-1 (ELOVL1) as key player, and its relevance to X-ALD.

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