Adrenoleukodystrophy in Norway: High Rate of De Novo Mutations and Age-Dependent Penetrance
Abstract
To investigate X-linked adrenoleukodystrophy in an unselected population, we performed a population based, cross-sectional prevalence study, supplemented by a retrospective study of deceased subjects. Sixty-three subjects (34 males, 29 females) belonging to 22 kindreds were included. Thirty-nine subjects (13 males, 26 females) were alive, and 24 (21 males, 3 females) were deceased on the prevalence day. The point prevalence of X-linked adrenoleukodystrophy in Norway on July 1, 2011, was 0.8 per 100,000 inhabitants. The incidence at birth in the period 1956-1995 was 1.6 per 100,000 inhabitants. An age-dependent penetrance was observed among males and females, with more severe phenotypes appearing with rising age. Only 5% of deceased males had not developed cerebral leukodystrophy. No female older than 50 years was neurologically intact. Sixteen mutations in the ABCD1 gene were identified. De novo mutations were found in 19% of probands. The frequency of X-linked adrenoleukodystrophy was lower in Norway than reported in the literature. A more severe natural course than previously reported was observed, indicating a need for better follow-up of both male and female patients. Given the high rate of de novo mutations, identification programs such as newborn screening may be required to offer timely treatment to all patients.
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Prevalence rates of around 1:200,000 for males and 1:100,000 for females were estimated for the Dutch and Norwegian populations.
“In addition to incidence rates, prevalence rates of around 1:200,000 for males and 1:100,000 for females were estimated by thorough investigations carried out for the Dutch and the Norwegian populations.14,21”
From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [14]
AMN has near 100% lifetime penetrance; all male and possibly most female patients will develop at least some symptoms of AMN late in life.
“It was recently reported that all male and possibly even most female patients will develop at least some symptoms of AMN late in life and thus AMN has a near 100% lifetime penetrance.12,14,23”
From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [14]
Horn et al. found a combined incidence rate of 1:61,000 for males plus females in the Norwegian population.
“Further, the study of Horn et al for the first time also directly addressed the number of affected females and found a combined incidence rate of 1:61,000 for males plus females in the Norwegian population.14”
From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [14]
A recent population-based Norwegian study reported a higher de novo mutation rate of at least 19%.
“However, a recent population-based Norwegian study reported a higher de novo mutation rate of at least 19%.14”
From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [14]
Cites
von Elm, E., Altman, D. G., Egger, M., Pocock, S. J., Gøtzsche, P. C., Vandenbroucke, J. P., & Initiative, F. T. S. (2007) · PLoS Medicine · doi:10.1371/journal.pmed.0040296 · Cited by 23,020 · see citing works
von Elm, E., Altman, D. G., Egger, M., Pocock, S. J., Gøtzsche, P. C., & Vandenbroucke, J. P. (2007) · Preventive Medicine · doi:10.1016/j.ypmed.2007.08.012 · Cited by 2,698 · see citing works
Moser, H. W., Mahmood, A., & Raymond, G. V. (2007) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0421 · Cited by 663 · see citing works
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
Adrenoleukodystrophy: Incidence, new mutation rate, and results of extended family screening
Bezman, L., Moser, A. B., Raymond, G. V., Rinaldo, P., Watkins, P. A., Smith, K. D., Kass, N. E., & Moser, H. W. (2001) · Annals of Neurology · doi:10.1002/ana.101 · Cited by 324 · see citing works
Symptoms in carriers of adrenoleukodystrophy relate to skewed X inactivation
Maier, E. M., Kammerer, S., Muntau, A. C., Wichers, M., Braun, A., & Roscher, A. A. (2002) · Annals of Neurology · doi:10.1002/ana.10376 · Cited by 72 · see citing works
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Adrenoleukodystrophy—Neuroendocrine pathogenesis and redefinition of natural history
Kemp, S., Huffnagel, I. C., Linthorst, G. E., Wanders, R. J., & Engelen, M. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.90 · Cited by 275 · see citing works
Berger, J., Wiesinger, C., & Eichler, F. (2015) · The Application of Clinical Genetics · doi:10.2147/tacg.s49590 · Cited by 140 · see citing works
van Engen, C. E., Ofman, R., Dijkstra, I. M. E., van Goethem, T. J., Verheij, E., Varin, J., Vidaud, M., Wanders, R. J. A., Aubourg, P., Kemp, S., et al. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.07.006 · Cited by 26 · see citing works
- Authors
- Horn, M. A., Retterstøl, L., Abdelnoor, M., Skjeldal, O. H., & Tallaksen, C. M. E.
- Affiliations
- Oslo University Hospital (NO)
- Vestre Viken Hospital Trust (NO)
- Venue
- Pediatric Neurology
- Publisher
- Elsevier BV
- Published
- 2013-03
- Volume
- 48
- Issue
- 3
- Pages
- 212-219
- ISSN
- 0887-8994 (ISSN-L)
- OpenAlex
- W1967220181
- Cited by
- 41
- References
- 6
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 4 · 2015: 4 · 2014: 5
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pediatric Neurology (publishedVersion)
- PubMed (publishedVersion)
- 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, ABCD1 gene, de novo mutations, age-dependent penetrance, prevalence, incidence, natural history (disease), newborn screening, Norway
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily D, Member 1, Adolescent, Adrenoleukodystrophy, Adult, Age Factors, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Mutation, Norway, Phenotype, Retrospective Studies, Incidence, Prevalence, Survival Rate, ATP-Binding Cassette Transporters, Penetrance
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