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Cited by 239Metabolism and Genetic DisordersLysosomal Storage Disorders ResearchHereditary Neurological Disorders

Adrenoleukodystrophy: Phenotypic variability and implications for therapy

Moser, H. W., Moser, A. B., Smith, K. D., Bergin, A., Borel, J., Shankroff, J., Stine, O. C., Merette, C. +3 more·1992·Journal of Inherited Metabolic Disease
DOI 10.1007/bf01799621
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Abstract

Summary: X‐linked adrenoleukodystrophy (ALD) is a relatively common disorder that shows a great deal of phenotypic variability. Approximately half of the patients have the rapidly progressive childhood cerebral form that is associated with an inflammatory response in brain and leads to total disability or death during the first decade. Twenty five per cent or more of the patients have adrenomyeloneuropathy (AMN), a form that progresses slowly, involves the spinal cord mainly, shows little or no inflammatory response, manifests in adulthood, and is compatible with a near‐normal life span. The two forms of the disease occur frequently within the same kindreds and nuclear families. Segregation analysis based on 3862 individuals in 89 kindreds points to the existence of an autosomal modifier locus with a likelihood ratio of 20:1. In addition, we present preliminary results of three types of therapy. Two hundred and four patients have received a dietary regimen that combines the administration of oils containing mono‐unsaturated fatty acids (oleic and erucic) with the restricted intake of very long‐chain fatty acids. This regimen normalizes the levels of satured very long‐chain fatty acids in plasma within 4 weeks. It appears to improve peripheral nerve function in patients with AMN, and a large‐scale trial is in progress to determine whether it can prevent the onset of neurological involvement in patients who have the biochemical abnormality of ALD but are neurologically intact. We report early results of bone marrow transplantation in 14 patients. There is encouraging but still preliminary evidence that transplantation can arrest the progression of the disease in patients with mild neurological involvement. There is urgent need to develop methods to combat the rapid progression of the cerebral forms of the disease, which so far has resisted therapeutic intervention, including immunosuppression or the administration of immunoglobulin.

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  • Early-stage treatment of childhood cerebral ALD with hematopoietic stem cell transplantation and, more recently, gene therapy can arrest disease progression if performed in the window of opportunity when the MRI is abnormal but neurological symptoms are not yet apparent.

    “Early-stage treatment of childhood cerebral ALD with hematopoietic stem cell transplantation and, more recently, gene therapy can arrest disease progression if performed in the window of opportunity when the MRI is abnormal but neurological symptoms are not yet apparent [7,38,43,44,45,46,47,48,49,50].”

    From Structure and Function of the ABCD1 Variant Database: 20 Years, 940 Pathogenic Variants, and 3400 Cases of Adrenoleukodystrophy (2022) · cites this paper as [44]

  • A large segregation analysis suggested the presence of a single major autosomal modifier locus in X-ALD.

    “Although a large segregation analysis suggested the presence of a single “major” autosomal modifier locus [111], attempts to identify a modifier variant among 16 candidate genes, including some involved in inflammatory processes, had no success [15,112,113,114,115,116], as reviewed in [15].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [111]

  • Segregation analysis based on 3,862 individuals from 89 kindreds suggested the presence of an autosomal modifier locus.

    “Indeed, segregation analysis based on 3,862 individuals from 89 kindreds suggested the presence of an autosomal modifier locus.96”

    From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [96]

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Authors
Moser, H. W., Moser, A. B., Smith, K. D., Bergin, A., Borel, J., Shankroff, J., Stine, O. C., Merette, C., Ott, J., Krivit, W., & Shapiro, E.
Affiliations
  • Johns Hopkins University (US)
  • The Departments of Psychiatry and Genetics and Development Columbia University USA
  • Columbia University (US)
  • University of Minnesota (US)
ORCID
Venue
Journal of Inherited Metabolic Disease
Publisher
Wiley
Published
1992-07
Volume
15
Issue
4
Pages
645-664
ISSN
  • 0141-8955 (ISSN-L)
  • 1573-2665
DOI
10.1007/bf01799621
OpenAlex
W2106485907
Cited by
239
References
4
Citations by year
2026: 1 · 2025: 4 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 4 · 2015: 3 · 2014: 3 · 2013: 7 · 2012: 1
FWCI
4.58
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Inherited Metabolic Disease (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Center for Research Resources (RR 000 52)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD24061, HD-10981, P30HD024061, P01HD010981)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords
X-linked adrenoleukodystrophy, phenotypic variability, adrenomyeloneuropathy, segregation analysis, dietary therapy, very long chain fatty acids, monounsaturated fatty acids, bone marrow transplantation, disease progression, immunosuppression, immunoglobulin therapy
MeSH terms
Adolescent, Adrenoleukodystrophy, Adult, Aged, Humans, Middle Aged, Phenotype, X Chromosome, Bone Marrow Transplantation

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