GM2-gangliosidosis, AB variant

GM2-gangliosidosis, AB variant is a rare inherited disorder that causes progressive destruction of nerve cells in the brain and spinal cord. It has a similar pathology to Sandhoff disease and Tay-Sachs disease.

Signs and symptoms of the AB variant begin in infancy. Infants with this disorder typically appear normal until the age of 3 to 6 months, when development slows and muscles used for movement weaken. Affected infants lose motor skills such as turning over, sitting, and crawling. As the disease progresses, infants develop seizures, vision and hearing loss, mental retardation, and paralysis. An eye abnormality called a cherry-red spot, which can be identified with an eye examination, is characteristic of this disorder. Children with the AB variant usually live only into early childhood.

Mutations in the GM2A gene cause GM2-gangliosidosis, AB variant. The GM2A gene provides instructions for making a protein called the GM2 activator. This protein is required for the normal function of beta-hexosaminidase A, a critical enzyme in the nervous system that breaks down a fatty substance called GM2 ganglioside. If mutations disrupt the activity of the GM2 activator, beta-hexosaminidase A cannot perform its normal function. As a result, GM2 ganglioside can accumulate to toxic levels in the brain and spinal cord. Progressive damage caused by the buildup of GM2 ganglioside leads to the destruction of nerve cells, which causes the severe medical problems characteristic of the AB variant. This condition is inherited in an autosomal recessive pattern.