Clinical, biochemical and molecular findings in 16 patients with GAMT deficiency

Objective: Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine synthesis, resulting in creatine deficiency and in accumulation of guanidinoacetate (GAA) in brain and body fluids. The symptoms and the severity of this disease are variable. In this study we analyzed clinical, biochemical and molecular findings in 16 patients with GAMT deficiency.

Patients and methods: Clinical, biochemical and molecular data were collected from reports in the literature, written medical reports and questionnaires. The main clinical manifestations (mental retardation, epilepsy and motor handicap) were scored, in order to assess the severity of the disease phenotype.

Results and conclusion: Age of onset was between 3 and 24 months. Mental retardation and seizures are the common clinical, the accumulation of GAA in body fluids and cerebral creatine deficiency the common biochemical denominators. GAMT deficiency can be divided into the three groups (severe with severe mental retardation and drug resistant seizures; moderate with moderate mental retardation and drug responsive seizures; and mild with mental retardation and occasional seizures). There was no correlation between severity of the clinical phenotype and the different mutations found in the patients. In patients with mental retardation and epilepsy, GAA in urine and in the blood spots should be determined as screening for the exclusion of GAMT deficiency.

Keywords: guanidinoacetate methyltransferase deficiency, guanidinoacetate