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Cited by 35Metabolism and Genetic DisordersHereditary Neurological DisordersLysosomal Storage Disorders Research

Neurological impairment among heterozygote women for X-linked Adrenoleukodystrophy: a case control study on a clinical, neurophysiological and biochemical characteristics

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Habekost, Clarissa Troller, Schestatsky, Pedro, Torres, Vitor Felix, de Coelho, Daniella Moura, Vargas, Carmen Regla, Torrez, Vitor, Oses, Jean Pierre, Portela, Luis Valmor +3 more·2014·Orphanet Journal of Rare Diseases
DOI 10.1186/1750-1172-9-6PMC PMC3896743
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Abstract

BACKGROUND: Neurologic impairments in female heterozygotes for X-linked Adrenoleukodystrophy (X-ALD) are poorly understood. Our aims were to describe the neurological and neurophysiological manifestations of a cohort of X-ALD heterozygotes, and to correlate them with age, disease duration, mutations, X-inactivation and serum concentrations of a marker of neuronal damage, neuron-specific enolase (NSE). METHODS: All 45 heterozygotes identified in our region, with previous VLCFA and molecular diagnosis, were invited to be evaluated through myelopathy scales JOA and SSPROM, nerve conduction studies and somatosensory evoked responses. X inactivation pattern was tested by HUMARA methylation assay. Serum NSE was measured by eletrochemiluminescense. RESULTS: Thirty three heterozygote women were recruited: 29 (87%) were symptomatic. Symptomatic and asymptomatic women presented different m ± sd ages (43.9 ± 10.2 versus 24.3 ± 4.6), JOA (14.5 ± 1.7 versus 16.6 ± 0.2) and SSPROM (86.6 ± 7.9 versus 98.4 ± 1.1) scores (p<0.05). Both JOA (r=-0.68) and SSPROM (r=-0.65) correlated with age, irrespectively of the disease status (p=0.0001, Spearman). Delayed latencies in the central ascending conduction studies on the lower limbs were present in 72% of all heterozygotes, and correlated with SSPROM (r=-0.47, p=0.018, Spearman). NSE values were higher in heterozygote than in control women (12.9 ± 7 and 7.2 ± 7 ng/ml, p=0.012, Mann-Whitney U). Mutation severity and inactivation patterns were not associated with neurologic status. CONCLUSION: Neurologic manifestations, clearly related to age, were quite common in the present cohort. JOA and SSPROM scales were able to discriminate the asymptomatic from the symptomatic heterozygotes. Both scales might be useful tools to follow disease progression, in future studies.

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  • Women with ALD develop myeloneuropathy, whereas men can develop all three core syndromes.

    “Women develop myeloneuropathy; men can develop all 3 syndromes.7-9”

    From International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy (2022) · cites this paper as [9]

    The Background reports that some women with X-ALD develop myeloneuropathy resembling adrenomyeloneuropathy. It also names cerebral ALD and adrenomyeloneuropathy as male phenotypes, but does not identify three core syndromes or state that men can develop all three. The indexed copy provides no page numbers for these passages. (LLM, conf=0.86)

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  • A high number, if not all, heterozygous females develop at least some symptoms of AMN, and the severity of symptoms increases with age.

    “During recent more detailed studies, it became apparent that a high number, if not all, of the heterozygous females develop at least some symptoms of AMN and that the severity of symptoms increases with age.12,24,89”

    From The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis (2015) · cites this paper as [89]

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Authors
Habekost, C. T., Schestatsky, P., Torres, V. F., de Coelho, D. M., Vargas, C. R., Torrez, V., Oses, J. P., Portela, L. V., Pereira, F. D. S., Matte, U., & Jardim, L. B.
Affiliations
  • Universidade Federal do Rio Grande do Sul (BR)
  • Universidade Católica de Pelotas (BR)
  • Hospital de Clínicas de Porto Alegre (BR)
Corresponding author
Jardim, Laura Bannach
ORCID
Venue
Orphanet Journal of Rare Diseases
Publisher
Springer Science and Business Media LLC
Published
2014-01-13
Volume
9
Issue
1
Pages
6-6
ISSN
1750-1172 (ISSN-L)
DOI
10.1186/1750-1172-9-6
PMC
PMC3896743
OpenAlex
W2110599418
Cited by
35
References
4
Citations by year
2026: 1 · 2025: 4 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 5 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 4 · 2014: 2
FWCI
2.77
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Orphanet Journal of Rare Diseases (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (publishedVersion, other-oa)
  • Americanae (AECID Library) (submittedVersion, cc-by-nc-sa)
Funders
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico
  • Hospital de Clínicas de Porto Alegre
  • Fundação Instituto de Pesquisas Econômicas
  • Instituto Nacional de Genética Médica Populacional
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
X-linked adrenoleukodystrophy, female heterozygotes, neurological deficit, myelopathy, JOA score, nerve conduction studies, somatosensory evoked potentials, neuron-specific enolase, X chromosome inactivation, very long chain fatty acids, mutation severity, disease progression
MeSH terms
Adrenoleukodystrophy, Adult, Female, Heterozygote, Humans, Middle Aged, Nervous System Diseases, Case-Control Studies

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