Evidence map›Paper›PMID 40775643›Full record

ArticleOrphanet journal of rare diseases2025

Establishing a core outcome set for creatine transporter deficiency and guanidinoacetate methyltransferase deficiency.

Zahra Nasseri Moghaddam, Emily K Reinhardt, Audrey Thurm, Beth K Potter, Maureen Smith, Celeste Graham, Beth H Tiller, Steven A Baker, Deborah A Bilder, Regina Bogar and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Orphanet journal of rare diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors.

Zahra Nasseri Moghaddam *Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
Emily K Reinhardt *Board of Directors & Staff, Association for Creatine Deficiencies, Carlsbad, CA, USA. registry@creatineinfo.org.ORCID http://orcid.org/0009-0009-1771-8768
Audrey ThurmNational Institute of Mental Health, NIH, Bethesda, MD, USA.
Beth K PotterSchool of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Maureen SmithPatient Partner, University of Ottawa, Ottawa, ON, Canada.
Celeste GrahamBoard of Directors & Staff, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Beth H TillerPatient/Caregiver Partner, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Steven A BakerDepartment of Pathology, University of Utah, Salt Lake City, UT, USA.
Deborah A BilderHuntsman Mental Health Institute, University of Utah, Salt Lake City, UT, USA.
Regina BogarPatient/Caregiver Partner, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Jacobus BritzPatient/Caregiver Partner, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Rachel CaffertyPatient/Caregiver Partner, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Daniel P CollerBoard of Directors & Staff, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Ton J DeGrauwScientific Medical Advisory Board, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Vicky HallPatient/Caregiver Partner, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Gerald S LipshutzDavid Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA.
Nicola LongoScientific Medical Advisory Board, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Saadet Mercimek-AndrewsScientific Medical Advisory Board, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Judith S MillerDepartment of Child and Adolescent Psychiatry and Behavioral Sciences, Center for Autism Research, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Marzia PasqualiScientific Medical Advisory Board, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Gajja S SalomonsScientific Medical Advisory Board, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Andreas SchulzeScientific Medical Advisory Board, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Celine P WheatonPatient/Caregiver Partner, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Kayla F WilliamsPatient/Caregiver Partner, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Sarah P YoungScientific Medical Advisory Board, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Jasmine LiDepartment of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
Sofia BalogBoard of Directors & Staff, Association for Creatine Deficiencies, Carlsbad, CA, USA.
Theresa SeluckyFine Point Consulting, Los Angeles, CA, USA.
Sylvia Stöckler-Ipsiroglu *Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
Heidi Wallis *Board of Directors & Staff, Association for Creatine Deficiencies, Carlsbad, CA, USA.

Funding

Neurodevelopmental and Behavioral Phenotyping ZICMH002961 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI THURM, AUDREY · 2017 to 2025
$12.6M
Intramural NIH HHS ZIC MH002961NIMH NIH HHS ZIC MH002961Patient-Centered Outcomes Research Institute EACB-23059
6 · The paper itself

Abstract

backgroundCreatine transporter (CTD) and guanidinoacetate methyltransferase (GAMT) deficiencies are rare inborn errors of creatine metabolism, resulting in cerebral creatine deficiency. Patients with either condition commonly exhibit intellectual and developmental disabilities, often accompanied by behavior problems, delayed speech, seizures, and motor impairments. There is currently no efficacious treatment for CTD, while current management for GAMT requires lifelong treatment with a protein restricted diet and intake of high amounts of oral supplements. Efforts to conduct clinical trials on potential treatments for these disorders are made more difficult by the lack of clinical and patient-derived meaningful outcomes. A core outcome set (COS) can facilitate consistent use of outcomes in studies. The current effort included patient and caregiver perspectives into the outcome selection of a COS for CTD and GAMT.

resultsWe partnered with caregivers and health professionals to establish the first COS for CTD and GAMT. The COS developed includes seven outcomes ("Adaptive Functioning", "Cognitive Functioning", "Emotional Dysregulation", "MRS Brain Creatine", "Seizure/Convulsions", "Expressive Communication", and "Fine Motor Functions") for both CTD and GAMT, and an additional outcome for GAMT ("Serum/Plasma Guanidinoacetate") that are important to stakeholders and consequently should be considered for measurement in every clinical trial. Caregivers were valued partners throughout the COS development process, which increased community engagement and facilitated caregiver empowerment.

conclusionsDevelopment of this COS illustrates a patient-centered approach for clinical trial readiness for CTD and GAMT that if utilized will make clinical trial results comparable, minimize bias in clinical trial outcome selection, and promote efficient use of resources.

Indexed as

Brain Diseases, Metabolic, InbornGuanidinoacetate N-MethyltransferaseMembrane Transport ProteinsMovement DisordersPlasma Membrane Neurotransmitter Transport ProteinsX-Linked Intellectual DisabilityChildCreatineFemaleHumansLanguage Development DisordersMaleCreatinecreatine transporterGuanidinoacetate N-MethyltransferaseMembrane Transport ProteinsPlasma Membrane Neurotransmitter Transport ProteinsCore outcome set (COS)Creatine transporter deficiencyGuanidinoacetate methyltransferase deficiencyPatient-centered researchPatient focused drug developmentRare disease

Identifiers

PMID40775643
PMCPMC12333098

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.