Guanidinoacetate methyltransferase deficiency

Guanidinoacetate methyltransferase deficiency is an inherited disorder that primarily affects the nervous system and muscles. This disorder usually appears in the first few months of life, when development of new motor and cognitive skills becomes delayed or stops. Eventually, affected children may lose previously acquired skills such as head control or sitting unsupported.

People with guanidinoacetate methyltransferase deficiency have a wide spectrum of neurological symptoms. In addition to intellectual disability and muscle weakness, some children with this disorder experience seizures. They may also develop autistic behaviors that affect communication and social interaction. Some affected children exhibit certain involuntary movements (extrapyramidal dysfunction) such as tremors or facial tics.

Guanidinoacetate methyltransferase deficiency is a very rare disorder. Only a few dozen 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 synthesis of the compound creatine from the protein building blocks (amino acids) glycine, arginine and methionine. Specifically, guanidinoacetate methyltransferase controls the second step of the sequence, in which creatine is produced from another compound called guanidinoacetate.

GAMT gene mutations impair the ability of the guanidinoacetate methyltransferase enzyme to participate in creatine synthesis. Creatine is needed for many tissues in the body to store and use energy properly, and the effects of guanidinoacetate methyltransferase deficiency are most severe in organs and tissues that require large amounts of energy, such as the brain and muscles.

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.