GAMT gene mutations damage the ability of the guanidinoacetate methyltransferase enzyme to contribute in creatine synthesis.
Guanidinoacetate methyltransferase deficiency (GAMT) is a genetic disorder that first and foremost affects the nervous system and muscles. Guanidinoacetate methyltransferase deficiency creatine biosynthesis imperfection, leads to depletion of creatine and phosphocreatine, and accumulation of guanidinoacetate in brain. Creatine in the person body is derived from two sources: the diet and endogenous synthesis. These disorders generally show in the first few months of life, when development of new motor and cognitive skills becomes delayed or stops. Finally, affected children may drop previously acquired skills such as head manage or sitting unsupported.
Community with guanidinoacetate methyltransferase deficiency has a broad spectrum of neurological symptoms. In addition to mental retardation and muscle weakness many kids with this disorder skill seizures. They may also grow autistic behaviors that affect communication and social interaction. Several affected children show certain involuntary movements such as tremors or facial tics. 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 glycine, arginine and methionine.
Creatine is required for various tissues in the body to accumulate and employ energy properly, and the effects of guanidinoacetate methyltransferase deficiency are most severe in organs and tissues that need large amounts of power, such as the brain and muscles. The parents of an individual with an autosomal recessive condition each carry one copy of the changed gene, but they typically do not appear signs and symptoms of the condition. The combination of creatine supplementation and a guanidinoacetate-lowering therapeutic approach resulted in improvement of clinical symptoms and metabolite concentrations in brain, muscle, and body fluids.
