T–Z

Tay-Sachs disease An inherited genetic disorder
that causes a progressive, fatal form of gangliosido-
sis (the accumulation of gangliosides within NERVE
cells). Tay-Sachs disease involves mutations of a
pair of genes on CHROMOSOME15 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 METABOLISMcannot
take place, and the GM2 ganglioside that enters the
cell accumulates. GM2 ganglioside concentrations
are highest within the nerve cells in the BRAINas
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 invol-
untary functions throughout the body. Tay-Sachs
disease is usually fatal before age five years. An
uncommon variation, late-onset Tay-Sachs dis-
ease, allows slight amounts of hex-A, delaying the
onset of symptoms until ADOLESCENCE or early
adulthood. However, the progressive loss of neu-
rological and cognitive function follows a similar
timeline once symptoms start.

Symptoms and Diagnostic Path
The earliest indication of Tay-Sachs disease is a
characteristic round, cherry-red spot on the mac-
ula 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 MUSCLEtone (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, BLOODtests to measure the level of

hex-A present in the circulation, and GENETIC TEST-

INGsuch as cytogenetic analysis and DNAsequenc-

ing. The genetic tests provide the definitive

diagnosis.

Treatment Options and Outlook

There is no treatment or cure for Tay-Sachs dis-

ease. Nearly all children who have Tay-Sachs dis-

ease 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 MUTA-

TION.

Risk Factors and Preventive Measures

Tay-Sachs disease is an autosomal recessive disor-

der, 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

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