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Longitudinal Characterization of Males With X-Linked Creatine Transporter Deficiency: Final Results of a Multiyear Observational Study

2025· article· en· W4415704440 on OpenAlexaff
Judith S. Miller, Cristan Farmer, Susan Blair, Simona Bianconi, Natacha Akshoomoff, Irina Anselm, Bruce A. Barshop, Lindsey Becker, Amanda Bennett, Leandra N. Berry, Elizabeth Berry‐Kravis, Aleksandra K. Bruchey, Anna W. Byars, Tricia Cimms, Kim M. Cecil, Maxine Covello, Laura S. Cubit, Tanvi Das, Robert J. Davis, Madison Drye, Can Fıçıcıoğlu, Robin P. Goin‐Kochel, W. Spencer Guthrie, Barbara Hallinan, Fady Hannah‐Shmouni, Kristin Gustafson, Dwight D. Koeberl, Nicola Longo, Eva Mamak, Saadet Mercimek‐Andrews, Claire Michalak, Forbes D. Porter, Samar Rahhal, Linda Rees, Gail A. Spiridigliozzi, Caitlin Stone, Nancy Sullivan, V. Reid Sutton, Rebecca P. Thomas, Manisha D. Udhnani, Susan E. Waisbren, Zhi Xu, Lin Zhang, Melanie Brandabur, Audrey Thurm

Bibliographic record

VenuePediatric Neurology · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetics and Neurodevelopmental Disorders
Canadian institutionsUniversity of Alberta HospitalUniversity of TorontoHospital for Sick Children
FundersUniversity of Utah HealthNational Institute of Child Health and Human DevelopmentNational Center for Advancing Translational SciencesNational Institute of Mental HealthUniversity of California, San DiegoEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentUltragenyx Pharmaceutical
KeywordsObservational studyTransporterCreatineCTDClinical neurology

Abstract

fetched live from OpenAlex

BACKGROUND: The purpose of the Vigilan observational study (ClinicalTrials.gov, NCT02931682) was to prospectively assess the natural history and developmental course of creatine transporter deficiency (CTD). METHODS: Males with CTD aged 6 months to 65 years were evaluated at 6-month intervals for up to 4 years. Evaluations included neurodevelopmental assessments of intellectual functioning, adaptive functioning, challenging behaviors and the onset and progression of medical comorbidities. RESULTS: Fifty participants (median age, 7.6 years) were enrolled. The predominant CTD phenotype consisted of significant intellectual disabilities and limited skill development over time. Most participants had a history of febrile or nonfebrile seizures, gastrointestinal symptoms, and growth failure. All participants learned how to walk, 78% developed at least some verbal speech, and 34% communicated using phrases or sentences. Norm-referenced neurodevelopment assessments indicated declining standardized scores over time; however, absolute scores (i.e., age equivalent person ability scores) indicated that developmental gains were slower than average, particularly among older participants. Between-person differences in neurodevelopmental skills as a function of age did not match within-person change, suggesting a cohort effect. CONCLUSIONS: In this cohort, CTD was associated with significant and persistent intellectual disability. The use of absolute metrics from neurodevelopmental tests (e.g., person ability scores) allowed for the quantification of slow, but present, skill development.

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 score0.178
Threshold uncertainty score0.410

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 head0.030
GPT teacher head0.257
Teacher spread0.227 · 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

Citations1
Published2025
Admission routes1
Has abstractyes

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