Guanidinoacetate methyltransferase deficiency: the first inborn error of creatine metabolism in man

Am J Hum Genet. 1996 May;58(5):914-22.


In two children with an accumulation of guanidinoacetate in brain and a deficiency of creatine in blood, a severe deficiency of guanidinoacetate methyltransferase (GAMT) activity was detected in the liver. Two mutant GAMT alleles were identified that carried a single base substitution within a 5' splice site or a 13-nt insertion and gave rise to four mutant transcripts. Three of the transcripts encode truncated polypeptides that lack a residue known to be critical for catalytic activity of GAMT. Deficiency of GAMT is the first inborn error of creatine metabolism. It causes a severe developmental delay and extrapyramidal symptoms in early infancy and is treatable by oral substitution with creatine.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Base Sequence
  • Child, Preschool
  • Creatine / metabolism*
  • Female
  • Guanidinoacetate N-Methyltransferase
  • Humans
  • Infant
  • Male
  • Metabolism, Inborn Errors / genetics
  • Metabolism, Inborn Errors / metabolism*
  • Metabolism, Inborn Errors / physiopathology
  • Methyltransferases / deficiency*
  • Methyltransferases / genetics
  • Molecular Sequence Data
  • Mutation


  • Methyltransferases
  • GAMT protein, human
  • Guanidinoacetate N-Methyltransferase
  • Creatine

Associated data

  • GENBANK/X90526