Definition:
In a normal lysosome, a protein called GM2 ganglioside activator and an enzyme known as beta-hexosaminidase A work together to break down a fatty substance called GM2 ganglioside.  If there is a mutation in the GM2 ganglioside activator, the enzyme beta-hexosaminidase A cannot break down the fatty substance.  Hence, the GM2 ganglioside accumulates in the central nervous system. The accumulation of GM2 ganglioside causes progressive destruction of the nerve cells in the brain and spinal cord and gives rise to the symptoms associated with this disorder.

 Activator Deficiency/GM2 Gangliosidosis is a very rare disorder affecting one child per 320,000 live births.

Symptoms:
The symptoms of Activator Deficiency/GM2 Gangliosidosis appear in infancy at around six months of age.  At this age, motor skills begin to decline and muscles begin to weaken. The affected child’s ability to turn over, to crawl or sit also begins to decline.  A startled response to noise and cherry-red spot in the eye are additional features of this disorder.  As the condition progresses, seizures, mental retardation, vision and hearing loss, as well as paralysis, may also occur.

Inheritance Pattern:
Activator Deficiency/GM2 Gangliosidosis is an autosomal recessive disorder.

Diagnosis and Testing:
Activator Deficiency/GM2 Gangliosidosis is detected by assaying beta-hexosaminidase A in the blood. Prenatal genetic screening is also available if one family member is affected with the disease.

Life Expectancy:
Life expectancy is approximately three years of age.

Treatment:
Currently, there is no cure for Activator Deficiency/GM2 Gangliosidosis. Anti-seizure medication can be administered to control seizure episodes.  One drug under investigation inhibits the synthesis of the gangliosides or the fatty substance that accumulates in the brain and spinal cord.  It is the hope that as research continues to explore treatment possibilities, a cure will be found for Activator Deficiency/GM2 Gangliosidosis.