Autosomal recessive inborn error of metabolism of creatine synthesis, caused by mutations of the GAMT gene at chromosome 19p13.3. Guanidinoacetic acid (GAA) is methylated by GAMT to form creatine. All of these patients present with global developmental delay, 60% of whom have severe symptoms. 75% of patients will develop seizures. 30% of patients will develop a movement disorder manifested by dystonia, choreoathetosis, hemiballismus, or ataxia.
Increased T2 signal in the globus pallidi will be seen in less than 50% of patients who have a movement disorder. MRS may show an absence of the Creatine peak. The diagnosis is confirmed by direct sequencing of GAMT (c.327 G>A panethine, c.59 G>C in Mediterranean countries)