Cerebral adrenoleukodystrophy (ALD) in only one of monozygotic twins with an identical ALD genotype
Abstract
We report on monozygotic twins with different clinical phenotypes of X‐linked adrenoleukodystrophy. At the age of 10 years both boys were neurologically asymptomatic. The first cranial magnetic resonance examination showed normal findings in the first twin and parietooccipital demyelination in the second. The latter developed behavioral problems 9 months later, followed by visual impairment and gait ataxia. His cranial magnetic resonance image at the age of 11 years showed progressive demyelination. In contrast, neurological status and magnetic resonance images remained normal in the first twin. The same point mutation in exon 8 of the adrenoleukodystrophy gene (C2203T) was detected in both boys. All genotype examinations were consistent with the diagnosis of monozygotic twins, suggesting that some nongenetic factors may be important for different adrenoleukodystrophy phenotypes.
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The few studied monozygotic twins with X-ALD showed less discordant phenotypes.
“Devastating childhood cALD and late adulthood AMN may co-exist within the same family [103,104,105,106], whereas the few studied monozygotic twins showed less discordant phenotypes [107,108,109,110].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [107]
Reports of varying phenotypes in identical twins suggest that environmental factors may be involved in X-ALD phenotypic variation.
“However, reports of varying phenotypes in identical twins suggest that environmental factors may be involved [Sobue et al., 1994;Korenke et al., 1996].”
From ABCD1 mutations and the X-linked adrenoleukodystrophy mutation database: Role in diagnosis and clinical correlations (2001) · cites this paper as Korenke et al., 1996
Even in monozygotic twins, different clinical phenotypes of X-ALD have been observed.
“Thirdly, even in monozygotic twins, different clinical phenotypes have been observed.34”
From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [34]
Cites
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Kemp, S., Pujol, A., Waterham, H. R., van Geel, B. M., Boehm, C. D., Raymond, G. V., Cutting, G. R., Wanders, R. J. A., & Moser, H. W. (2001) · Human Mutation · doi:10.1002/humu.1227 · Cited by 332 · see citing works
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“This is also supported by the development of different clinical phenotypes in monozygotic twins [135,136] and the observation that moderate head trauma can initiate cerebral demyelination in AMN patients [137,138].”
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X-linked adrenoleukodystrophy phenotype is independent of ABCD2 genotype
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Immune response of BV-2 microglial cells is impacted by peroxisomal beta-oxidation
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Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy
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- Authors
- Korenke, G. C., Wilichowski, E., Hunneman, D. H., Hanefeld, F., Fuchs, S., Krasemann, E., & Doerr, H. G.
- Affiliations
- University of Göttingen (DE)
- Universität Hamburg (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Corresponding author
- Hanefeld, Folker
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 1996-08
- Volume
- 40
- Issue
- 2
- Pages
- 254-257
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2006924544
- Cited by
- 117
- References
- 1
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 9 · 2023: 4 · 2022: 7 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 12 · 2017: 4 · 2016: 5 · 2015: 2 · 2014: 2 · 2013: 2 · 2012: 4
- FWCI
- 3.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- cerebral adrenoleukodystrophy, X-linked adrenoleukodystrophy, monozygotic twins, genotype-phenotype discordance, non-genetic factors, behavioral problems, visual impairment, gait ataxia
- MeSH terms
- Adrenoleukodystrophy, Brain, Child, Demyelinating Diseases, Diseases in Twins, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Pedigree, Twins, Monozygotic
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