Marion Austria

2014

August 1,

MEB 32
Tay-Sachs disease
1. What is the nature of the disease?
Tay-Sachs is a rare hereditary disease caused by a genetic
mutation that leaves the body unable to produce an enzyme (known as
Hex-A) necessary for fat metabolism in nerve cells. Without this
enzyme, central nervous system degeneration ensues. The destructive
process begins in the fetus early in pregnancy, although the disease is
not clinically apparent until the child is several months old. By the time
a child with TSD is three or four years old, the nervous system is so
badly affected that life itself cannot be supported. Even with the best
of care, all children with classical TSD die early in childhood, usually by
the age of five.
In infants, Tay-Sachs is characterized by progressive mental
deterioration, blindness, paralysis, epileptic seizures, and death,
usually between ages two and five. Late-onset Tay-Sachs occurs in
persons who have a genetic mutation that is similar but allows for
some production of the missing enzyme.
To date, there is no cure or effective treatment for TSD. However,
there is active research being done in many investigative laboratories
in the U.S. and around the world. The uses of enzyme replacement
therapy to provide the Hex-A which is missing in babies with TSD has
been explored. Although this approach is promising, scientists still face
serious obstacles. Because the disease affects brain cells which are
protected by the blood-brain barrier, enzymes like Hex-A are blocked
from entering the brain from the blood. Bone marrow transplantation
has also been attempted but to date has not been successful in
reversing or slowing damage to the central nervous system in babies
with TSD.

2. What happens when an individual has this disease? What are the signs
and symptoms?

Most babies with classic Tay-Sachs Disease are born happy and
seemingly healthy. There is typically no indication of any signs of
illness. The first 6 to 9 months of life have all of the typical ups and
downs familiar to most parents: smiling, crying, sleepless nights, latenight feeds, learning to roll over, beginning to babble, starting solid
foods, laughing with delight, and cooing peacefully.

Then, typically by 6 to 9 months of age:

The baby begins to make less and less eye contact with the
parents.
There is an exaggerated startle response to noise. In retrospect,
many parents recall that their baby had always been sensitive to
loud noises.
They sometimes learn to sit up or even stand
They may begin to speak several words.

The babies, who had been developing normally, now begin to lag
behind. They still grow and develop, but the milestones all come a bit
late. This is usually when parents start worrying that something is
wrong.
By 12 to 16 months:

Babies usually lost the ability to stand, to sit, and even to

vocalize.
increasing loss of coordination
progressive inability to swallow
breathing difficulties

From there, the deterioration is relentless. Seizures typically begin

in the second year. Before long, the toddler is completely blind and
non-communicative. Progressive spasticity is interrupted by
convulsions.
Symptoms:

Deafness

Decreased eye contact, blindness

Decreased muscle tone (loss of muscle strength)

Delayed mental and social skills

Dementia
Increased startle reaction
Irritability
Listlessness
Loss of motor skills
Paralysis or loss of muscle function
Seizures

3. Can the defect in cellular organelle reversible?

Increase in survival rate can be observed only when the
therapeutic genes are expressed either before the disease is apparent
or during its early manifestations. However, irrespective of when
treatment was administered, widespread and abundant expression of
-hexosaminidase with consequent clearance of glycoconjugates, synuclein and ubiquitinated proteins, and abrogation of inflammatory
responses and neuronal loss will be observed. Also defects in
myelination occur in early life and cannot be easily resolved when
treatment is given to the adult brain resulting the defect in cellular
organelle to be irreversible. These indicate that there is a limited
temporal opportunity in which function and survival can be improvedbut regardless of resolution of the cardinal pathological features of
GM2 gangliosidosis, a point is reached when functional deterioration
and death cannot be prevented.
4. Is there a repair mechanism? If yes, discuss. If no, why?
There is no cure for Tay-Sachs. Treatment is supportive and aims
to manage the symptoms.Treatment typically consists of keeping the
patient comfortable. This is called palliative care. Palliative care may
include medication for pain or to control seizures, physical therapy,
feeding tubes, and respiratory care to reduce mucus buildup in
the lungs. Respiratory difficulties are improved by chest physiotherapy.
Massages and physical therapy can help to promote relaxation and
flexibility. Anti-epileptic drugs are used to control seizures.
Several approaches to treat GM2 gangliosidosis diseases are being investigated. One, called Enzyme Replacement Therapy, consists of

the administration of artificial enzyme to replace the missing or nonfunctional enzyme. Due to its large size, the enzyme is not able to pass
the blood-brain barrier to reach its target in the brain, and it is not efficiently taken up by nerve cells. This approach has not been successful
yet.
Gene therapy is one of the advance therapy, which involves the
introduction of the normal gene, is currently under investigation in animal and cell models. Molecular Chaperone therapy is also being explored through clinical trials.