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

Sylvia Stockler-Ipsiroglu*, Clara van Karnebeek, Nicola Longo, G. Christoph Korenke, Saadet Mercimek-Mahmutoglu, Iris Marquart, Bruce Barshop, Christiane Grolik, Andrea Schlune, Brad Angle, Helena Caldeira Araújo, Turgay Coskun, Luisa Diogo, Michael Geraghty, Goknur Haliloglu, Vassiliki Konstantopoulou, Vincenzo Leuzzi, Alina Levtova, Jennifer MacKenzie, Bruno MarandaAizeddin A. Mhanni, Grant Mitchell, Andrew Morris, Theresa Newlove, Deborah Renaud, Fernando Scaglia, Vassili Valayannopoulos, Francjan J. van Spronsen, Krijn T. Verbruggen, Nataliya Yuskiv, William Nyhan, Andreas Schulze

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)16-25
Number of pages10
JournalMolecular Genetics and Metabolism
Issue number1
StatePublished - 2014


  • Autism
  • Creatine deficiency
  • Magnetic resonance spectroscopy
  • Neurodevelopmental outcome
  • Speech delay
  • Treatment evidence

ASJC Scopus subject areas

  • Genetics
  • Endocrinology
  • Molecular Biology
  • Biochemistry
  • Endocrinology, Diabetes and Metabolism


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