Guanidinoacetate methyltransferase deficiency

Guanidinoacetate methyltransferase deficiency is an inherited disorder that primarily affects the brain and muscles. People with this disorder have intellectual disability that is usually severe, with speech development limited to a few words. Almost all individuals with guanidinoacetate methyltransferase deficiency experience recurrent seizures (epilepsy). Most develop autistic behaviors that affect communication and social interaction; some affected individuals also exhibit self-injurious behaviors such as head-banging. Certain involuntary movements (extrapyramidal dysfunction) such as tremors or facial tics occur in about half of affected individuals.

People with guanidinoacetate methyltransferase deficiency may have weak muscle tone and delayed development of motor skills such as sitting or walking. In severe cases they may lose previously acquired skills such as the ability to support their head or to sit unsupported.

Guanidinoacetate methyltransferase deficiency is a very rare disorder. About 80 affected individuals have been reported worldwide. Of these, approximately one third are of Portuguese origin.

Mutations in the GAMT gene cause guanidinoacetate methyltransferase deficiency. The GAMT gene provides instructions for making the enzyme guanidinoacetate methyltransferase. This enzyme participates in the two-step production (synthesis) of the compound creatine from the protein building blocks (amino acids) glycine, arginine, and methionine. Specifically, guanidinoacetate methyltransferase controls the second step of this process. In this step, creatine is produced from another compound called guanidinoacetate. Creatine is needed for the body to store and use energy properly.

GAMT gene mutations impair the ability of the guanidinoacetate methyltransferase enzyme to participate in creatine synthesis, resulting in a shortage of creatine. The effects of guanidinoacetate methyltransferase deficiency are most severe in organs and tissues that require large amounts of energy, especially the brain.

Read more about the GAMT gene.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.