Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Feb;80(1):52-72.
doi: 10.1002/jdn.10003. Epub 2020 Jan 26.

X-linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies

Bela R Turk  1 , Christiane Theda  2 , Ali Fatemi  1 , Ann B Moser  1
Affiliations
Review

X-linked adrenoleukodystrophy: Pathology, pathophysiology, diagnostic testing, newborn screening and therapies

Bela R Turk et al. Int J Dev Neurosci. 2020 Feb.

Abstract

Adrenoleukodystrophy (ALD) is a rare X-linked disease caused by a mutation of the peroxisomal ABCD1 gene. This review summarizes our current understanding of the pathogenic cell- and tissue-specific roles of lipid species in the context of experimental therapeutic strategies and provides an overview of critical historical developments, therapeutic trials and the advent of newborn screening in the USA. In ALD, very long-chain fatty acid (VLCFA) chain length-dependent dysregulation of endoplasmic reticulum stress and mitochondrial radical generating systems inducing cell death pathways has been shown, providing the rationale for therapeutic moiety-specific VLCFA reduction and antioxidant strategies. The continuing increase in newborn screening programs and promising results from ongoing and recent therapeutic investigations provide hope for ALD.

Keywords: X-linked adrenoleukodystrophy; clinical trials; inflammation; newborn screening; therapy; very long-chain fatty acids.

PubMed Disclaimer

Conflict of interest statement

Ali Fatemi, MD is on the safety monitoring board for Bluebird Bio, Stealth Biotherapeutics and a paid consultant to Calico Laboratories. Christiane Theda, MD, PhD is the Co‐Founder, Chief Medical Officer and a Company Director of Navi Medical Technologies Pty Ltd and Medical Advisor to Ventora Pty Ltd. These companies develop new biomedical devices unrelated to peroxisomal disorders and adrenoleukodystrophy. Bela R. Turk, MD and Ann B. Moser, BA have no conflict of interest.

Figures

Figure 1
Figure 1
ALD newborn screening in the USA as of October 19, 2019 (https://adrenoleukodystrophy.info)
See this image and copyright information in PMC

References

    1. Anchisi, L. , Dessi, S. , Pani, A. , & Mandas, A. (2012). Cholesterol homeostasis: A key to prevent or slow down neurodegeneration. Frontiers in Physiology, 3, 486. - PMC - PubMed
    1. Asheuer, M. , Bieche, I. , Laurendeau, I. , Moser, A. , Hainque, B. , Vidaud, M. , & Aubourg, P. (2005). Decreased expression of ABCD4 and BG1 genes early in the pathogenesis of X‐linked adrenoleukodystrophy. Human Molecular Genetics, 14, 1293–1303. 10.1093/hmg/ddi140 - DOI - PubMed
    1. Aubourg, P. (2015). Cerebral adrenoleukodystrophy: A demyelinating disease that leaves the door wide open. Brain, 138, 3133–3136. - PubMed
    1. Aubourg, P. , Adamsbaum, C. , Lavallard‐Rousseau, M.‐C. , Rocchiccioli, F. , Cartier, N. , Jambaque, I. , … Bougneres, P.‐F. (1993). A two‐year trial of oleic and erucic acids (“Lorenzo's oil”) as treatment for adrenomyeloneuropathy. New England Journal of Medicine, 329, 745–752. 10.1056/NEJM199309093291101 - DOI - PubMed
    1. Aubourg, P. R. , Sack, G. H., Jr. , & Moser, H. W. (1988). Frequent alterations of visual pigment genes in adrenoleukodystrophy. American Journal of Human Genetics, 42, 408–413. - PMC - PubMed

MeSH terms

Substances