Mutations in the GAMT gene are a relatively rare cause of creatine deficiency syndrome. Affected individuals may demonstrate cerebral creatine deficiency on MR spectroscopy and high GAA in urine. Guanidinoacetate methyltransferase deficiency is inherited in an autosomal recessive manner and is caused by biallelic mutations in the GAMT gene. This gene maps to 19p13.3 and is involved in the biosynthesis of creatine. Individuals with GAMT deficiency typically present with severe intellectual disabilities and seizure disorders which may be resistant to drug therapy. Behavioral problems, including autistic behaviors and self-mutilation are common, and pyramidal/extrapyramidal symptoms affect about one-half of patients with GAMT deficiency. Dietary management of GAMT deficiency via manipulation of critical amino acids may improve clinical outcome.