GAMT deficiency of ... (Guanidinoacetate methyltransferase deficiency) - Gen GAMT

GAMT deficiency, also called GAMT deficiency is an inherited disorder that affects the brain and muscles. Without early treatment, people affected develop neurological problems that are often severe. These issues include intellectual disability, speech development limited to a few words, and frequent episodes of epilepsy. Affected individuals may also manifest autistic behaviors that affect communication and social interaction or self - injurious behavior such as head banging. Other features of GAMT deficiency may include extrapyramidal dysfunction, which can manifest itself through tremors and facial tics. In addition, people with GAMT deficiency may have weak muscle tone and delayed development of motor skills. In severe cases, affected individuals may lose previously acquired skills as the ability to support the head or sit up unassisted.

This process is due to mutations in the gene GAMT (guanidinoacetate N-methyltransferase), located on the short arm of chromosome 19 (19p13.3). The gene encodes GAMT GAMT enzyme which is primarily expressed in the liver. This enzyme is involved in the synthesis of creatine compound from glycine, arginine and methionine amino acids. Specifically, GAMT controls the second step of this process. In this step, creatine is produced from another compound called guanidinoacetate. Creatine is needed in the body to store and use energy properly. It is involved in supplying energy for muscle contraction and is also important in the nervous system. Besides its role in the synthesis of creatine, it is believed that guanidinoacetate methyltransferase enzyme helps activate the oxidation process of fatty acids. This process provides an energy source for cells during times of stress when glucose is scarce.

They have been described at least 49 mutations in the gene responsible GAMT deficiency GAMT. Most affected individuals of Portuguese descent have a particular mutation in which the amino acid tryptophan by the amino acid serine at position 20 replaced in the enzyme (Trp20Ser or W20S). Mutations in the gene GAMT adversely affect the ability of the GAMT enzyme involved in the synthesis of creatine, which leads to a deficiency of creatine. The effects of GAMT deficiency are more severe in the organs and tissues that require large amounts of energy, especially the brain.

This disease is inherited in an autosomal recessive pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with GAMT deficiency, by complete PCR amplification of the exons of the gene GAMT, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).