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Record W4413889205 · doi:10.1002/jmd2.70042

Metabolic Control and Frequency of Clinical Monitoring Among Canadian Children With Phenylalanine Hydroxylase Deficiency: A Retrospective Cohort Study

2025· article· en· W4413889205 on OpenAlexafffundabout
Nataliya Yuskiv, Ammar Saad, Beth K. Potter, Sylvia Stöckler‐Ipsiroglu, John J. Mitchell, Steven Hawken, Kylie Tingley, Michael Pugliese, Monica Lamoureux, Andrea Chow, Jonathan B. Kronick, Kumanan Wilson, Annette Feigenbaum, Sharan Goobie, Michal Inbar‐Feigenberg, Julian Little, Saadet Mercimek‐Andrews, Amy Pender, Chitra Prasad, Andreas Schulze, Yannis Trakadis, Gloria Ho, Hilary Vallance, Valerie Austin, Anthony Vandersteen, Andrea C. Yu, Cheryl R. Greenberg, Aizeddin A. Mhanni, Pranesh Chakraborty

Bibliographic record

VenueJIMD Reports · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMetabolism and Genetic Disorders
Canadian institutionsUniversity of ManitobaLondon Health Sciences CentreMcMaster Children's HospitalUniversity of AlbertaChildren's Hospital Research Institute of ManitobaNova Scotia Health AuthorityIzaak Walton Killam Health CentreBruyèreChildren's Hospital of Eastern OntarioMcGill UniversityMcGill University Health CentreUniversity of OttawaOttawa HospitalWestern UniversityUniversity of TorontoMontreal Children's HospitalDalhousie UniversitySickKids FoundationBC Children's HospitalHospital for Sick ChildrenUniversity of British Columbia
FundersCanadian Institutes of Health Research
KeywordsHyperphenylalaninemiaPhenylalanine hydroxylaseMetabolic control analysisMedicinePhenylalanineRetrospective cohort studyCohortPediatricsInternal medicineEndocrinologyBiologyInsulinBiochemistry

Abstract

fetched live from OpenAlex

ABSTRACT Achieving and maintaining metabolic control is critical for children with phenylalanine hydroxylase (PAH) deficiency. This retrospective longitudinal cohort study investigated metabolic control and monitoring frequency of children with PAH deficiency (≤ 12 years) treated at one of 12 pediatric metabolic centres across Canada. We abstracted data from medical charts and analyzed outcomes by age and diagnostic classification, using mixed effects regression. Of 215 children included in the study, 43% had a chart diagnosis of classic phenylketonuria (PKU); the remainder had a diagnosis of mild PKU or mild hyperphenylalaninemia (grouped as “less severe PAH deficiency”). During the first month of life, blood phenylalanine levels of children with classic PKU reached the target therapeutic range of 120–360 μmol/L at a median age of 15 days, but 74.3% and 32.9% had ≥ 1 and ≥ 3 values below 120 μmol/L, respectively. From age > 1 month to 12 years, mean blood phenylalanine values were 260.6 and 236.7 μmol/L for children with classic PKU and less severe PAH deficiency, respectively, with a trend of increased blood phenylalanine levels with increasing age (p < 0.001). Fewer children with classic PKU (37.2%) versus less severe PAH deficiency (77.9%) had > 60% of values in the therapeutic range, indicating less optimal metabolic control. Frequency of blood phenylalanine testing and communication with metabolic centres decreased with age. Our findings suggest a need to better understand the reasons for blood phenylalanine variability across child age and disease severity in order to inform supports for children with PAH deficiency and their caregivers to maintain metabolic control.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.003
Version: metacan-v3-hybrid-931329e0061cValidation 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 score0.047
Threshold uncertainty score0.094

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.001
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0020.005
Science and technology studies0.0020.001
Scholarly communication0.0010.000
Open science0.0010.001
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.005
GPT teacher head0.259
Teacher spread0.255 · 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 source (direct Gemma or distilled Codex), 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

Citations0
Published2025
Admission routes3
Has abstractyes

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