Adrenoleukodystrophy in female heterozygotes: underrecognized and undertreated
Abstract
X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease resulting from mutations in the gene ABCD1 and alterations in peroxisomal beta-oxidation of long chain fatty acids. As it has been frequently discussed, it manifests a wide range of phenotypes in male, with progressive myelopathy being the most common. Even though the gene is localized to the X-chromosome and a region subject to X-inactivation, female carriers still are affected significantly by this condition. It has been stated that between 20 and 50% of women who are carriers may manifest some symptoms and recent evidence has suggested the differences in disease manifestations and relative rates of progression between men and women. However there have been only limited studies specifically addressing this and to date there has been no comprehensive review discussing the different phenotypes in female carriers, as well as the differences in disease onset, progression, disability, nervous system pathology and neuroimaging patterns compared to affected males. This is of key importance as similarities and differences between genders will assist in determining how best to target therapies in all affected individuals as opportunities for treatment present themselves. As will be further addressed in this review, we need to improve our understanding of the associations of emergent neuroimaging techniques to physical disability in this population. We reviewed the clinical presentations in the carrier population, the distinct disability profile and neuroimaging findings in order to put together pieces of this neglected segment in X-ALD and give direction to further studies.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PAI remains exceedingly uncommon in heterozygous females.
“Although studies on female X-ALD patients are few in number, PAI remains an exceedingly uncommon condition in heterozygous females (29–31).”
From X-linked adrenoleukodystrophy and primary adrenal insufficiency (2023) · cites this paper as [31]
Cites
Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-Linked Adrenoleukodystrophy
Cartier, N., Hacein-Bey-Abina, S., Bartholomae, C. C., Veres, G., Schmidt, M., Kutschera, I., Vidaud, M., Abel, U., Dal-Cortivo, L., Caccavelli, L., et al. (2009) · Science · doi:10.1126/science.1171242 · Cited by 1,508 · 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
Self-citationKemp, 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
Self-citationAdrenoleukodystrophy: 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
Self-citationA Two-Year Trial of Oleic and Erucic Acids (“Lorenzo's Oil”) as Treatment for Adrenomyeloneuropathy
Aubourg, P., Adamsbaum, C., Lavallard-Rousseau, M.-C., Rocchiccioli, F., Cartier, N., Jambaque, I., Jakobezak, C., Lemaitre, A., Boureau, F., Wolf, C., et al. (1993) · New England Journal of Medicine · doi:10.1056/nejm199309093291101 · Cited by 242 · see citing works
Moser, H. W., Loes, D. J., Melhem, E. R., Raymond, G. V., Bezman, L., Cox, C. S., & Lu, S.-E. (2000) · Neuropediatrics · doi:10.1055/s-2000-9236 · Cited by 210 · see citing works
Self-citationSymptoms 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
Seven-Tesla proton magnetic resonance spectroscopic imaging in adult X-linked adrenoleukodystrophy
Ratai, E., Kok, T., Wiggins, C., Wiggins, G., Grant, E., Gagoski, B., O’Neill, G., Adalsteinsson, E., & Eichler, F. (2008) · Archives of Neurology · doi:10.1001/archneur.65.11.1488 · Cited by 37 · see citing works
Cerebral X‐linked adrenoleukodystrophy in a girl with Xq27‐Ter deletion
Hershkovitz, E., Narkis, G., Shorer, Z., Moser, A. B., Watkins, P. A., Moser, H. W., & Manor, E. (2002) · Annals of Neurology · doi:10.1002/ana.10248 · Cited by 30 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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
X-linked adrenoleukodystrophy in women: A cross-sectional cohort study
Engelen, M., Barbier, M., Dijkstra, I. M. E., Schür, R., de Bie, R. M. A., Verhamme, C., Dijkgraaf, M. G. W., Aubourg, P. A., Wanders, R. J. A., van Geel, B. M., et al. (2014) · Brain · doi:10.1093/brain/awt361 · Cited by 234 · see citing works
X-Linked Adrenoleukodystrophy: Pathogenesis and Treatment
Engelen, M., Kemp, S., & Poll-The, B.-T. (2014) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-014-0486-0 · Cited by 187 · 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
Peroxisomal ABC Transporters: An Update
Tawbeh, A., Gondcaille, C., Trompier, D., & Savary, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22116093 · Cited by 68 · see citing works
“Female carriers usually remain quasi asymptomatic or present only a mild phenotype, but severe forms have also been described [86].”
BackgroundX-linked adrenoleukodystrophy and primary adrenal insufficiency
Cappa, M., Todisco, T., & Bizzarri, C. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1309053 · Cited by 28 · see citing works
- Authors
- Jangouk, P., Zackowski, K. M., Naidu, S., & Raymond, G. V.
- Affiliations
- Kennedy Krieger Institute (US)
- Corresponding author
- Jangouk, Parastoo
- Venue
- Molecular Genetics and Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-02
- Volume
- 105
- Issue
- 2
- Pages
- 180-185
- ISSN
- 1096-7192 (ISSN-L)
- OpenAlex
- W2043136531
- Cited by
- 63
- References
- 9
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 11 · 2020: 4 · 2019: 4 · 2018: 1 · 2017: 4 · 2016: 4 · 2015: 4 · 2014: 7 · 2013: 6 · 2012: 4
- FWCI
- 0.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular Genetics and Metabolism (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, female carriers, ABCD1 gene, peroxisomal beta-oxidation, long-chain fatty acids, disease progression, physical disability, neuroimaging findings, underdiagnosis
- MeSH terms
- ATP Binding Cassette Transporter, Subfamily D, Member 1, Adrenoleukodystrophy, Fatty Acids, Female, Heterozygote, Humans, Male, Mutation, Sex Characteristics, ATP-Binding Cassette Transporters, Chromosomes, Human, X, Neuroimaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
