GM3 synthase deficiency (GM3 synthase deficiency) - Gen ST3GAL5.

GM3 synthase deficiency is a disorder characterized by epilepsy and problems with brain development. Within the first few weeks after birth, newborn infants become irritable and have difficulty eating and vomiting that prevent them grow and gain weight at the usual pace. In addition, in the first year of life begin seizures that worsen over time. Are possible multiple types of seizures, including tonic-clonic generalized seizures that cause muscle stiffness, seizures and unconsciousness. Some affected children also have episodes of convulsive status epilepticus. Seizures associated with GM3 synthase deficiency tend to be refractory to treatment with anticonvulsant drugs.

This disease intensely altered brain development. Most affected children have severe intellectual disabilities and do not develop skills such as reaching, talk, sit unsupported, or walking. Some affected individuals have involuntary twisting or jerking movements of the arms described as choreoathetoid. Although newborns affected can probably see and hear at birth, as the disease progresses vision and hearing deteriorates. Some affected individuals have changes in pigmentation. These changes appear in childhood and can become more or less evident over time.

GM3 synthase deficiency is due to mutations in the gene ST3GAL5, located on the short arm of chromosome 2 (2p11.2). This gene encodes an enzyme called GM3 synthase. This enzyme carries out a chemical reaction is the first step in the production of gangliosides. Specifically, GM3 synthase converts a molecule lactosylceramide to a simple ganglioside GM3 called. Additional reactions used to generate more complex GM3 ganglioside. Gangliosides are present on the surface of cells and tissues throughout the body, and are particularly abundant in the nervous system. Although their exact roles are not clear, it is likely that these molecules help regulate chemical signaling pathways that influence the growth and proliferation, motility, adhesion and cell survival. Gangliosides appear to be important for the function and normal brain development.

It has identified at least one mutation in the gene ST3GAL5 leading to GM3 synthase deficiency. The known mutation replaces the amino acid arginine with an early stop signal in the protein coding (Arg288Ter or R288X, R232X or Arg232Ter), which prevents any encoding functional GM3 synthase. Without this enzyme, the cells can not produce GM3 gangliosides or other normally. However, it is not clear how the loss of this enzyme leads to the signs and symptoms of GM3 synthase deficiency. Work is underway to determine whether deficiency or an accumulation of ganglioside compounds used to generate ganglioside, or both, which underlies seizures and other problems with brain development associated with this disease.

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 GM3 synthase deficiency, by complete PCR amplification of the exons of the gene ST3GAL5, 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).