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

• Published in: International journal of developmental neuroscience Vol. 80; no. 1; pp. 52 - 72
• Main Authors: Turk, Bela R., Theda, Christiane, Fatemi, Ali, Moser, Ann B.
• Format: Journal Article
• Language: English
• Published: United States John Wiley and Sons Inc 01.02.2020
• Subjects: Adrenoleukodystrophy - diagnosis; ATP Binding Cassette Transporter, Subfamily D, Member 1 - genetics; clinical trials; Endoplasmic Reticulum Stress; Humans; Infant, Newborn; inflammation; Mutation; Neonatal Screening; newborn screening; therapy; very long‐chain fatty acids; X‐linked adrenoleukodystrophy; very long-chain fatty acids; clinical trials; inflammation; newborn screening; therapy; X-linked adrenoleukodystrophy
• ISSN: 0736-5748; 1873-474X; 1873-474X
• DOI: 10.1002/jdn.10003

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.