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Record W2099101508 · doi:10.1016/j.ymgme.2013.10.018

Guanidinoacetate methyltransferase (GAMT) deficiency: Outcomes in 48 individuals and recommendations for diagnosis, treatment and monitoring

2013· article· en· W2099101508 on OpenAlexafffund
Sylvia Stöckler‐Ipsiroglu, Clara van Karnebeek, Nicola Longo, Georg Christoph Korenke, Saadet Mercimek‐Mahmutoglu, Iris Marquart, Bruce A. Barshop, Christiane Grolik, Andrea Schlune, Brad Angle, Helena Caldeira, Turgay Coşkun, Luísa Diogo, Michael T. Geraghty, Göknur Haliloğlu, Vassiliki Konstantopoulou, Vincenzo Leuzzi, Alina Levtova, Jennifer MacKenzie, Bruno Maranda, Aizeddin A. Mhanni, Grant A. Mitchell, Andrew A. M. Morris, Theresa Newlove, Deborah L. Renaud, Fernando Scaglia, Vassili Valayannopoulos, Francjan J. van Spronsen, K. T. Verbruggen, Nataliya Yuskiv, William L. Nyhan, Andreas Schulze

Bibliographic record

VenueMolecular Genetics and Metabolism · 2013
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicMuscle metabolism and nutrition
Canadian institutionsUniversity of ManitobaUniversité de SherbrookeQueen's UniversityCentre Hospitalier Universitaire Sainte-JustineUniversity of OttawaUniversity of British ColumbiaHospital for Sick ChildrenUniversity of Toronto
FundersMedizinische Universität WienARUP LaboratoriesVrije Universiteit AmsterdamChildren's Hospital FoundationUniversiteit van AmsterdamUniversität WienBC Children's Hospital
KeywordsCreatineArginineDoseOrnithineMedicineInternal medicinePediatricsCreatine MonohydrateGastroenterologyEndocrinologyAmino acidBiochemistryBiologyPathology

Abstract

fetched live from OpenAlex

We collected data on 48 patients from 38 families with guanidinoacetate methyltransferase (GAMT) deficiency. Global developmental delay/intellectual disability (DD/ID) with speech/language delay and behavioral problems as the most affected domains was present in 44 participants, with additional epilepsy present in 35 and movement disorder in 13. Treatment regimens included various combinations/dosages of creatine-monohydrate, l-ornithine, sodium benzoate and protein/arginine restricted diets. The median age at treatment initiation was 25.5 and 39 months in patients with mild and moderate DD/ID, respectively, and 11 years in patients with severe DD/ID. Increase of cerebral creatine and decrease of plasma/CSF guanidinoacetate levels were achieved by supplementation with creatine-monohydrate combined with high dosages of l-ornithine and/or an arginine-restricted diet (250 mg/kg/d l-arginine). Therapy was associated with improvement or stabilization of symptoms in all of the symptomatic cases. The 4 patients treated younger than 9 months had normal or almost normal developmental outcomes. One with inconsistent compliance had a borderline IQ at age 8.6 years. An observational GAMT database will be essential to identify the best treatment to reduce plasma guanidinoacetate levels and improve long-term outcomes.

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 score0.006
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.001
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 head0.017
GPT teacher head0.280
Teacher spread0.263 · 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

Citations140
Published2013
Admission routes2
Has abstractyes

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