Funded in part by ARUP Laboratories
Arginine:glycine amidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide
Stockler-Ipsiroglu S, Apatean D, Battini R, DeBrosse S, Dessoffy K, Edvardson S, Eichler F, Johnston K, Koeller DM, Nouioua S, Tazir M, Verma A, Dowling MD, Wierenga KJ, Wierenga AM, Zhang V, Wong LJ
Molecular genetics and metabolism · 45 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Case report (classified by our AI screen)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Industry funded
- University or hospital
- Vanderbilt University
- Nonprofit
- Children's Hospital Foundation
- University or hospital
- BC Children's Hospital
- Company
- ARUP Laboratories
- Nonprofit
- BC Children's Hospital Foundation
Based on 5 listed funder(s).
Publication
- Published
- 2015-10-23 · Mol Genet Metab · vol. 116 · issue 4 · pp. 252–259
- Publisher
- Elsevier BV
- Cited
- 70 citations · more than 84% of similar papers · 1.9× the field average
- References
- 28 works
- Access
- Open access (hybrid journal) · CC-BY-NC-ND
- Research areas
- Muscle metabolism and nutrition · Metabolism and Genetic Disorders · Amino Acid Enzymes and Metabolism
- Keywords
- Medicine, Creatine, Missense mutation, Intellectual disability, Pediatrics, Internal medicine, Myopathy, Arginine, Asymptomatic, Biology, Psychiatry, Genetics, Mutation
- MeSH
- humans, muscular diseases, speech disorders, amino acid metabolism, inborn errors, creatine, amidinotransferases, glycine, treatment outcome, magnetic resonance spectroscopy, sequence analysis, dna, developmental disabilities, gene expression, protein structure, secondary, protein structure, tertiary, genes, recessive, mutation, models, molecular, adolescent, child, child, preschool, female, male, young adult, intellectual disability
17 authors
From CA, IT, US, IL, DZ
- Sylvia Stöckler‐Ipsiroglu · correspondingUniversity of British Columbia; BC Children's Hospital; Child and Family Research Institute
- Delia ApateanUniversity of British Columbia
- Roberta BattiniFondazione Stella Maris
- Suzanne D. DeBrosseUniversity Hospitals Cleveland Medical Center
- Kimberley DessoffyUniversity Hospitals Cleveland Medical Center
- Simon EdvardsonHadassah Medical Center
Abstract
Background
Arginine:glycine aminotransferase (AGAT) (GATM) deficiency is an autosomal recessive inborn error of creative synthesis.
Objective
We performed an international survey among physicians known to treat patients with AGAT deficiency, to assess clinical characteristics and long-term outcomes of this ultra-rare condition.
Results
16 patients from 8 families of 8 different ethnic backgrounds were included. 1 patient was asymptomatic when diagnosed at age 3 weeks. 15 patients diagnosed between 16 months and 25 years of life had intellectual disability/developmental delay (IDD). 8 patients also had myopathy/proximal muscle weakness. Common biochemical denominators were low/undetectable guanidinoacetate (GAA) concentrations in urine and plasma, and low/undetectable cerebral creatine levels. 3 families had protein truncation/null mutations. The rest had missense and splice mutations. Treatment with creatine monohydrate (100-800 mg/kg/day) resulted in almost complete restoration of brain creatine levels and significant improvement of myopathy. The 2 patients treated since age 4 and 16 months had normal cognitive and behavioral development at age 10 and 11 years. Late treated patients had limited improvement of cognitive functions.
Conclusion
AGAT deficiency is a treatable intellectual disability. Early diagnosis may prevent IDD and myopathy. Patients with unexplained IDD with and without myopathy should be assessed for AGAT deficiency by determination of urine/plasma GAA and cerebral creatine levels (via brain MRS), and by GATM gene sequencing.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY-NC-ND).
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