AMT

The AMT gene provides instructions for making an enzyme called aminomethyltransferase. This enzyme is one of four components (subunits) that make up a large complex called glycine cleavage enzyme. Within cells, this complex is active in specialized energy-producing centers called mitochondria.

As its name suggests, glycine cleavage enzyme processes a molecule called glycine by cutting (cleaving) it into smaller pieces. Glycine is an amino acid, which is a building block of proteins. This molecule also acts as a neurotransmitter, which is a chemical messenger that transmits signals in the brain. The breakdown of excess glycine is necessary for the normal development and function of nerve cells in the brain and spinal cord.

glycine encephalopathy - caused by mutations in the AMT gene

Mutations in the AMT gene are responsible for 10 percent to 15 percent of all cases of glycine encephalopathy. More than a dozen mutations have been identified in affected individuals. Most of these genetic changes alter single amino acids in aminomethyltransferase. Other mutations delete genetic material from the AMT gene or disrupt how genetic information from the gene is spliced together to make a blueprint for producing aminomethyltransferase.

AMT mutations alter the structure and function of aminomethyltransferase. When an altered version of this enzyme is incorporated into the glycine cleavage enzyme complex, it prevents the complex from breaking down glycine properly. As a result, excess glycine can build up to toxic levels in the body's organs and tissues. Damage caused by harmful amounts of this molecule in the brain and spinal cord is responsible for the intellectual disability, seizures, and breathing difficulties characteristic of glycine encephalopathy.