Early diagnosis of cerebral X-linked adrenoleukodystrophy in boys with Addison’s disease improves survival and neurological outcomes
Open accessAbstract
Approximately one third of boys with X-linked adrenoleukodystophy (X-ALD) develop an acute, progressive inflammatory process of the central nervous system, resulting in rapid neurologic deterioration and death. Hematopoietic cell transplantation (HCT) can halt the progression of neurologic disease if performed early in the course of the cerebral form of X-ALD. We describe a retrospective cohort study of 90 boys with X-ALD evaluated at our institution between 2000 and 2009, to determine if early diagnosis of X-ALD following the diagnosis of unexplained adrenal insufficiency (AI) improves outcomes. We describe seven cases with a delay in the diagnosis of X-ALD and compare their outcomes to ten controls with the diagnosis of ALD made within 12 months following diagnosis of AI. At the time of evaluation for HCT, boys with a delay in the diagnosis of X-ALD had more extensive cerebral involvement and more limited functioning. These boys also were 3.9 times more likely to die and had significant advancement of cerebral disease after HCT, compared with boys with a timely diagnosis of X-ALD. In conclusion, the early diagnosis of cerebral X-ALD following the diagnosis of unexplained AI, and subsequent treatment with HCT improves both neurological outcomes and survival in boys with cerebral X-ALD.
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In patients with subclinical adrenal insufficiency, monitoring and early initiation of hormone replacement therapy can avoid adrenal crises and life-threatening events.
“In addition, in patients with subclinical adrenal insufficiency, monitoring and early initiation of hormone replacement therapy can avoid adrenal crises and life-threatening events.30,67”
From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [67]
The Discussion (page unavailable) mentions monitoring boys with X-linked adrenoleukodystrophy for adrenal insufficiency, while the Methods describe testing adrenal function. The paper attributes improved survival and neurological outcomes to early diagnosis of cerebral disease and hematopoietic cell transplantation. Searches for hormone or steroid replacement and adrenal crises found no passage addressing whether early replacement therapy prevents crises or life-threatening events. (LLM, conf=0.74)
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Eichler, F., Duncan, C., Musolino, P. L., Orchard, P. J., De Oliveira, S., Thrasher, A. J., Armant, M., Dansereau, C., Lund, T. C., Miller, W. P., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1700554 · Cited by 604 · see citing works
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Kemper, A. R., Brosco, J., Comeau, A. M., Green, N. S., Grosse, S. D., Jones, E., Kwon, J. M., Lam, W. K. K., Ojodu, J., Prosser, L. A., et al. (2017) · Genetics in Medicine · doi:10.1038/gim.2016.68 · Cited by 109 · see citing works
- Authors
- Polgreen, L. E., Chahla, S., Miller, W., Rothman, S., Tolar, J., Kivisto, T., Nascene, D., Orchard, P. J., & Petryk, A.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Petryk, Anna
- Venue
- European Journal of Pediatrics
- Published
- 2011-01-29
- Volume
- 170
- Issue
- 8
- Pages
- 1049-1054
- ISSN
- 0340-6199 (ISSN-L)
- 1432-1076
- PMC
- PMC3101278
- OpenAlex
- W2156485773
- Cited by
- 49
- References
- 4
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2020: 2 · 2019: 7 · 2018: 1 · 2017: 6 · 2016: 2 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 5
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Pediatrics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of Minnesota
- National Institutes of Health (5k12rr023247-05)
- National Center for Research Resources (K12-RR023247, 5K12RR023247-05)
- Topics
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- X-linked adrenoleukodystrophy, early diagnosis, Addison's disease, adrenal insufficiency, hematopoietic stem cell transplantation, neurological outcome, survival, boys, delayed diagnosis, neurological deterioration
- MeSH terms
- Addison Disease, Adrenal Insufficiency, Adrenoleukodystrophy, Child, Child, Preschool, Humans, Infant, Male, Retrospective Studies, Cohort Studies, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Disease Progression, Early Diagnosis, Delayed Diagnosis
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