Arginine: Glycine amidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide

Sylvia Stockler-Ipsiroglu, Delia Apatean, Roberta Battini, Suzanne DeBrosse, Kimberley Dessoffy, Simon Edvardson, Florian Eichler, Katherine Johnston, David M. Koeller, Sonia Nouioua, Meriem Tazir, Ashok Verma, Monica D. Dowling, Klaas J. Wierenga, Andrea M. Wierenga, Victor Zhang, Lee Jun C. Wong

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)252-259
Number of pages8
JournalMolecular Genetics and Metabolism
Issue number4
StatePublished - 2015


  • Cerebral creatine deficiency
  • GATM
  • Intellectual disability
  • Myopathy

ASJC Scopus subject areas

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


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