Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive error of creatine synthesis characterized by cerebral creatine deficiency, accumulation of guanidinoacetate, mental retardation, epilepsy and extrapyramidal signs. Patients with GAMT deficiency have an unspecific but relatively constant clinical presentation.

We presented the behavioral and seizure related manifestations of two siblings with GAMT deficiency and compared their clinical phenotype to the related literature. Our patients, an 8-year and 14-year old boys with GAMT deficiency, presented mental retardation, epilepsy and autistic behaviour. Diagnosis was done by brain magnetic resonance spectroscopy, biochemical and genetic procedures (guanidinoacetate quantification, determination of GAMT activity and mutation analysis in the GAMT gene). GAMT gene was analyzed by DNA sequence analysis: the homozygous c.326A>G mutation was detected. This mutation is predicted to result in a missense mutation (one amino acid replacement) or in erroneous splicing. The mutation was not detected before in any other patient with GAMT deficiency or in 13000 other controls.

GAMT deficiency is treatable; therefore, its early diagnosis might be critical, to prevent irreversible brain damage. It must be considered in the differential diagnosis of the broad range of unexplained neuropsychiatric disorders  with epilepsy in children and it can be ruled out/detected by using brain magnetic resonance spectroscopy and/or by guanidinoacetate and creatine measurements in body fluids.