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Record W4413638354 · doi:10.1186/s13023-025-03987-8

The impact of vanishing white matter on unaffected family members

2025· article· en· W4413638354 on OpenAlexaff
Romy J. van Voorst, Daphne H. Schoenmakers, Irene van Beelen, Francesco Gavazzi, Alexandra Chapleau, Adeline Vanderver, Geneviève Bernard, Ingeborg Krägeloh‐Mann, Marjo S. van der Knaap

Bibliographic record

VenueOrphanet Journal of Rare Diseases · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA regulation and disease
Canadian institutionsMcGill UniversityMcGill University Health Centre
FundersNederlandse Organisatie voor Wetenschappelijk Onderzoek
KeywordsHuman geneticsWhite matterGeneticsBiologyMedicineGene

Abstract

fetched live from OpenAlex

BACKGROUND: Vanishing White matter (VWM) is one of the more prevalent leukodystrophies, caused by biallelic pathogenic variants in any of the EIF2B1-5 genes. It is characterized by chronic progressive neurological deterioration and additional stress-provoked episodes of rapid decline, leading to severe neurological impairment and early death. The impact of VWM on unaffected family members has not been investigated. METHODS: This international cross-sectional study enrolled parents, partners, and unaffected siblings. We used online administration of (1) health-related quality of life questionnaires (quantitative, comprising the EuroQol-5-Dimensions [EQ5-D]-5-Levels questionnaire [EQ-5D-5L], EuroQol-5-Dimensions-Youth-3-Levels questionnaire [EQ-5D-Y-3L], Pediatric Quality of Life Family Impact Module [PedsQL™-FIM], PedsQL™ Child-Adult Self Report [PedsQL™-SC]); (2) VWM-specific customized questionnaires (quantitative, comprising the impact of VWM inventory questionnaires for parents, partners and siblings); and (3) in-depth semi-structured interview (qualitative). RESULTS: A total of 100 family members were included: 52 mothers, 29 fathers, 13 unaffected siblings, and 6 partners. Mothers and partners scored significantly poorer on the EQ5D-5L than the reference norms. Fathers and mothers scored significantly poorer on the PedsQL™-FIM than the reference norms. Siblings scored similar to the reference norms on the EQ5D-5L and all domains of the PedsQL™-SC, with the lowest score on the emotional domain. Qualitative interviews revealed three main drivers of the impact of VWM: (1) lack of knowledge and empathy of healthcare professionals, (2) unpredictable disease course, and (3) caregiver responsibilities. Mothers reported substantial impacts on their emotional well-being and dissatisfaction with their professional development. Fathers commonly reported financial concerns and heightened family responsibility. Partners mentioned emotional exhaustion and difficulty in managing family responsibilities. Siblings frequently reported internal struggles, finding it challenging to express their feelings. CONCLUSIONS: Mothers and partners indicate a significant and consistent reduction in their quality of life on standardized questionnaires. Qualitative interviews revealed in-depth details of VWM's impact on all family members. Improved healthcare communication, symptom management resources, and support networks are essential for alleviating VWM's impact on families. This study emphasizes the importance of tailored approaches to supporting family members of VWM patients and enhancing their quality of life.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.487
Threshold uncertainty score0.277

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.006
GPT teacher head0.267
Teacher spread0.262 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations2
Published2025
Admission routes1
Has abstractyes

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