GM2 gangliosidosis, AB variant (GM2 gangliosidosis-AB variant) - Gen GM2A.
The GM2, AB variant, gangliosidosis is a rare inherited disorder that gradually destroys nerve cells in the brain and spinal cord. Signs and symptoms of variant AB manifest themselves in childhood. Affected children have an apparently normal development until age 3 to 6 months, when development slows down and skeletal muscles weaken. Affected children lose motor skills such as turning, sitting and crawling. Also they develop an exaggerated startle reaction to loud noises. As the disease progresses, children with AB variant have seizures, vision and hearing loss, mental retardation and paralysis. An eye abnormality is a cherry red spot is characteristic of this disease. In general, children with AB variant live only in early childhood.
This process is due to mutations in the gene GM2A, located on the long arm of chromosome 5 (5q33.1). This gene encodes a protein called GM2 ganglioside activator. This protein is required for the normal function of the enzyme beta-hexosaminidase A, which plays a critical role in the central nervous system. The enzyme beta-hexosaminidase A and GM2 ganglioside activator protein act together in lysosomes. In the lysosomes, the activator protein binds to a fatty substance called GM2 ganglioside and presents beta-hexosaminidase for decomposition.
Only a few mutations in the gene GM2A have been identified in people with Gangliosidosis GM2, AB variant. Some of these mutations change the amino acids in ganglioside GM2 activator. Other mutations remove a small amount of DNA GM2A gene. These genetic changes lead to an unstable protein which is rapidly degraded, or inhibit functional protein encoding. GM2 ganglioside activator without, beta-hexosaminidase A is unable to break GM2 ganglioside. Consequently, this substance accumulates to toxic levels, particularly in nerve cells in the brain and spinal cord. Progressive damage due to the accumulation of GM2 ganglioside leads to the destruction of these cells, which underlies the signs and symptoms of variant GM2 Gangliosidosis AB.
This disease is inherited in an autosomal recessive pattern, that is, 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 GM2 gangliosidosis AB variant, by complete PCR amplification of exons GM2A gene, 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).