Tay-Sachs disease AB variant

Tay-Sachs disease AB variant is an extremely rare, severe disorder affecting the nervous system, characterized by progressive neurological decline. At its core, the condition is caused by defects in the GM2A gene, which codes for the ganglioside activator protein involved in lipid metabolism. It primarily presents in infancy, with affected children experiencing significant developmental challenges. In terms of prevalence, this condition is very rare, affecting fewer than 1 in 1,000,000 people.

Affected individuals typically show signs of impaired neurological function from an early age. Characteristic features include the accumulation of GM2 gangliosides, marked hypotonia, myoclonic seizures, an exaggerated startle response, and global developmental delay. After a period of apparently typical early development, affected children experience a phase of developmental regression marked by loss of previously acquired skills, followed by stabilization or further neurological decline. Not all individuals experience all features, and severity varies considerably, with cognitive and developmental challenges being central to the condition.

Tay-Sachs disease AB variant is caused by pathogenic variants in the GM2A gene, which leads to a deficiency of the ganglioside activator protein. This deficiency interferes with the normal breakdown of GM2 gangliosides, resulting in their accumulation in the brain and other tissues, and ultimately causing neurodegeneration. The condition is inherited in an autosomal recessive pattern, meaning that a child must inherit two defective copies of the gene, one from each parent, to manifest the disease. This condition is more common when parents share a common ancestor, and genetic counseling is recommended to discuss carrier testing and recurrence risks for family members. Associated genes include GM2A.