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Tay-Sachs Disease Definition
An inherited genetic disorder that causes a progressive, fatal form of gangliosidosis (the accumulation of gangliosides within NERVE cells). Tay-Sachs disease involves mutations of a pair of genes on CHROMOSOME 15 that encode for the enzyme hexosaminidase-A (hex-A). The mutation blocks production of hex-A. The body requires hex-A to metabolize GM2 ganglioside, a fatty acid that nerve cells need to metabolize and produce energy.
Without adequate hex-A this METABOLISM cannot take place, and the GM2 ganglioside that enters the cell accumulates. GM2 ganglioside concentrations are highest within the nerve cells in the BRAIN as these nerve cells have the highest energy needs among nerve cells. GM2 ganglioside accumulates in other nerve cells as well. The accumulation causes the nerve cell to swell and eventually rupture.
Though the accumulation of GM2 ganglioside begins before birth, symptoms do not become apparent until age four to six months. Around this age the damage to brain tissue reaches a critical level and begins to disrupt brain activity. The child appears to regress developmentally. Brain function continues to decline, affecting intellectual and thought processes as well as voluntary and involuntary functions throughout the body.
Tay-Sachs disease is usually fatal before age five years. An uncommon variation, late-onset Tay-Sachs disease, allows slight amounts of hex-A, delaying the onset of symptoms until ADOLESCENCE or early adulthood. However, the progressive loss of neurological and cognitive function follows a similar timeline once symptoms start.
Symptoms of Tay-Sachs Disease and Diagnostic Path
The earliest indication of Tay-Sachs disease is a characteristic round, cherry-red spot on the macula at the back of the EYE, the point where the ocular nerve joins the RETINA. The spot represents the onset of gangliosidosis in the optic nerve. Other symptoms include
- flaccid MUSCLE tone (early)
- loss of voluntary muscle control and movement (late)
- irritability (early)
- intellectual impairment
- seizures (late)
- diminishing responsiveness and awareness (progressive)
- loss of vision (progressive)
The diagnostic path includes family history, ethnic heritage, BLOOD tests to measure the level of hex-A present in the circulation, and GENETIC TESTING such as cytogenetic analysis and DNA sequencing. The genetic tests provide the definitive diagnosis.
Tay-Sachs Disease Treatment Options and Outlook
There is no treatment or cure for Tay-Sachs disease. Nearly all children who have Tay-Sachs disease die before the age of five years. Research exploring methods to replace hex-A so far have been unsuccessful. Currently the most effective efforts target prevention by identifying carriers, who do not themselves have Tay-Sachs disease and who may not know they carry the GENE MUTATION.
Risk Factors and Preventive Measures
Tay-Sachs disease is an autosomal recessive disorder, meaning both parents must have the mutated gene for them to have a child with the disease, a one in four chance with each CONCEPTION. People at highest risk for Tay-Sachs disease are those of Ashkenazi Jewish heritage. A blood test became available in 1985 to detect carriers of Tay-Sachs disease, who do not themselves have the disease but who have lower than normal amounts of hex-A in their blood. GENETIC COUNSELING can help couples who are carriers make informed decisions about whether to have children. Assisted reproductive technologies (ARTs) such as in vitro fertilization allow genetic testing before implantation so the couple knows the conceived child does not carry the mutated genes.