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What is Tay-Sachs Disease
Tay-Sachs
disease is a progressive neurological genetic disorder
that appears in three forms:
Classic Infantile,
Juvenile
and Late Onset or Chronic
Tay-Sachs.
History:
The disease is named for
Warren Tay (1843-1927), a British ophthalmologist who in
1881 described a patient with a
cherry-red spot
on the retina of the eye.
It is also named for Bernard Sachs (1858-1944), a New
York neurologist whose work several years later provided
the first description of the cellular changes in Tay-Sachs
disease. Sachs also recognized the familial nature of
the disorder, and, by observing numerous cases, he noted
that most babies with Tay-Sachs disease at that time
were of Eastern European Jewish origin. Today, Tay-Sachs
occurs among people of all backgrounds.
Cause:
Tay-Sachs
disease is caused by the absence or insufficient level
of a vital enzyme called
Hexosaminidase A (Hex-A).
Without Hex-A, a fatty substance or lipid called
GM2 ganglioside accumulates
abnormally in cells, especially in the nerve cells of
the brain. This ongoing accumulation, also called “substrate,”
causes progressive damage to the cells. In
Classic Infantile
the destructive process begins in the fetus early in
pregnancy, although the disease is not clinically
apparent (symptoms do not start) until the child is
several months old. By the time a child with Tay-Sachs
disease 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
classic Tay-Sachs disease die early in childhood,
usually by the age of 5, although some do live longer.
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Fact:
Tay-Sachs Disease is
caused by the absence of a vital enzyme
called Hexosamindase A (Hex-A). |
To date, there is no cure or effective treatment for Tay-Sachs
disease. However, there is active
research being done in many investigative
laboratories in the U.S. and around the world exploring
a range of
therapeutic approaches. For the first time in
the history of the disease there currently are
clinical trials testing the potential of a
substrate reduction drug (miglustat) in all
three forms of Tay-Sachs, with the Late Onset trial
having started in 2002. The uses of
enzyme replacement therapy to provide the
Hex-A that is missing in babies with
classic infantile or significantly reduced in
children and adults with Tay-Sachs disease has been
explored but presents serious obstacles. Because the
disease affects brain cells that are protected by the
blood-brain barrier, enzymes such as Hex-A
are blocked from entering the brain by the blood. Stem
cell transplantation using umbilical cord blood is an
investigational procedure attempted with a small number
of very young children, but to date there is not enough
information for specific results about reversing or
slowing damage to the central nervous system in this
group with Tay-Sachs disease.
Gene therapy, molecular or
pharmacological chaperone therapy and
neural stem cell therapy are among those
potential treatments being researched.
Tay-Sachs carrier testing is vital for individuals in
high-risk populations: Ashkenazi Jews, French Canadians,
Louisiana Cajun, Pennsylvania Dutch and preliminary data
suggests persons of British Isle and Italian decent have
an increased carrier rate over the general population.
Carrier testing is best completed before conception.
Even if your childbearing years are over, your carrier
status can be an extremely important piece of
information. If you are a carrier, your close relatives
(children, brothers, sisters, cousins, aunts, uncles)
should be alerted so that they can be tested as well.
Tay-Sachs carrier testing is also vital for the close
relatives of families with an affected child, regardless
of ethnic background, since all parents of children with
Tay-Sachs are, by definition, carriers.
Although a cure for Tay-Sachs disease does not exist at
the present time, specific support, programs and
services for affected individuals and their families are
available through organizations such as National Tay-Sachs
& Allied Diseases Association, Inc. (NTSAD). |
Classic
Infantile Tay-Sachs
Classic Infantile Tay-Sachs is the most
common form of this rare disease and is characterized by very
little to no
Hexosaminidase-A (Hex-A) enzyme
activity. It is important to note that Tay-Sachs ‘breeds true in
a family,’ which means if a family has a child affected by
Classic Infantile Tay-Sachs their other children will only be at
risk for having Classic Infantile Tay-Sachs. One set of parents
could not have a child affected by Classic Infantile and
Juvenile or Late Onset Tay-Sachs.
A baby
with Tay-Sachs disease appears normal at birth and seems to
develop normally until about 6 months of age. The first signs of
Tay-Sachs disease can vary and are evident at different ages in
affected children. Initially, development slows, there is a loss
of peripheral vision, and the child exhibits an abnormal
startle response. By about 2 years of
age, most children experience recurrent
seizures and diminishing mental
function. The infant gradually regresses, losing skills one by
one, and is eventually unable to crawl, turn over, sit, or reach
out. Other symptoms include increasing loss of coordination,
progressive inability to swallow and breathing difficulties.
Eventually, the child becomes blind, mentally retarded,
paralyzed, and non-responsive to his or her environment.
Juvenile
Tay-Sachs
Tay-Sachs is caused by the absence of a
vital enzyme called
Hexosaminidase-A (Hex-A). Like most storage disorders, Tay-Sachs
disease occurs along a continuum. From infantile, the most
severe form in which there is virtually complete absence of
Hex-A, to Juvenile, which affects older children to
Late Onset Tay-Sachs (LOTS), impacting even older children
or teens and adults who have very low or moderately low levels
of Hex-A. Without any Hex-A, a fatty substance or lipid
accumulates abnormally in cells, especially in the nerve cells
of the brain. This ongoing build-up causes progressive damage to
the nerve cells, gradually leading to their degeneration and
death. Individuals who have low levels of Hex-A, have a slower
onset of symptoms and progression of disease, compared to those
with Classic Infantile Tay-Sachs. It is important to note that
within each form of Tay-Sachs disease, there is a range of
severity and each person’s experience with the disease is
distinctive.
Children with Juvenile Hex-A deficiency usually develop symptoms
between the ages of 2 and 5 years that resemble the symptoms of
the Classic Infantile form. Though the course of the disease is
slower, end stages generally occur in late adolescence or into
the 20s. If starting after age 5, symptoms may be milder than
those that characterize earlier onset forms. Mental abilities,
vision and hearing remain intact, but affected individuals
develop
ataxia (lack of coordination),
dysarthria (slurred speech),
muscle atrophy (weakness), muscle cramps, tremors,
unsteady gait and sometimes mental illness. Again, the
differences in age of onset and severity of symptoms shows the
broad range of this disease and why it continues to be a mystery
to even many seasoned medical professionals.
Late-Onset Tay-Sachs Disease
Late-onset Tay-Sachs (LOTS) disease is a
rare form of Tay-Sachs disease, a lysosomal storage disorder
caused by the absence of the enzyme
Hexosaminidase A (Hex-A). LOTS was first recognized in the
1970s during routine Tay-Sachs carrier screening.
Investigators have discovered very low
levels of Hex-A in older children and adults whose symptoms
include
ataxia (lack of coordination),
dysarthria (slurred speech) and
muscle
atrophy (weakness). Many of these individuals had been
misdiagnosed with other muscular or neurological disorders. It
is not uncommon for affected people to go many years before
receiving an accurate diagnosis of LOTS. Accurate diagnosis can
be made through
enzyme
assay and
DNA
analysis.
The symptoms typically presents in
adolescence, with dysarthria,
proximal
(trunk) muscle weakness, tremor and
ataxia.
Muscle cramps, especially in the legs at night, and
fasciculations (muscle twitching) are common. Not all
symptoms are present in every individual affected by the
disease; weakness of the proximal muscles, however, is a symptom
common to all. Examples of trunk muscle weakness may include
difficulty rising from a seated position, trouble getting out of
bed, struggling to balance while getting dressed. Symptoms of
manic-depression or
psychotic episodes may be present in about 30% of affected
persons.
As a recently recognized rare form along
the Tay-Sachs continuum, the course of LOTS is not completely
known. Life expectancy is probably not reduced. Affected
individuals understandably report feelings of isolation and
uncertainty as to what to anticipate as the disease progresses.
Social and academic difficulties, resulting from the physical
and psychiatric manifestations of the disease, are also a
concern.
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Fact:
LOTS affects adults,
not infants as in classical Tay-Sachs, who display a
significantly reduced level of Hex-A, rather than a
complete absence of the enzyme. |
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