Tay-Sachs disease – causes, symptoms, diagnosis, treatment, pathology

Tay-Sachs disease – causes, symptoms, diagnosis, treatment, pathology


Tay-Sachs disease, or TSD for short, is a
lysosomal storage disorder caused by a mutation in a gene on chromosome 15, which codes for
a lysosomal enzyme called beta-hexosaminidase A, or HEX-A for short. This enzyme normally
breaks down a lipid called GM2 ganglioside. GM2 is found mainly in neurons, so without
HEX-A, it accumulates inside lysosomes. TSD is also known as GM2 gangliosidosis, type
I. This results in progressive symptoms of central nervous system or CNS degeneration,
like decreased muscle tone, visual difficulties and seizures, which usually begin by 3 to
6 months of age, proceeding to death by age 4. TSD is an autosomal recessive genetic condition,
so males and females are affected equally, inheriting one mutated HEX-A gene from each
asymptomatic or heterozygous parent in order to develop the homozygous condition. This
also means that TSD tends to occur in isolated, inbred populations or communities, which accounts
for the predominant occurrence of the disease in infants of Ashkenazi Jewish heritage, and
in certain French Canadian, Amish, and Cajun populations. These mutations can result in either no synthesis,
or defective synthesis of HEX-A, resulting in either a total deficiency of HEX A or varying
degrees of enzyme activity depending on the specific mutation. So with some mutations,
GM2 accumulates over a longer period of time, accounting for a more gradual onset of CNS
symptoms in some people. Depending on age of onset, TSD can be infantile,
with onset at 3 to 6 months; juvenile, with onset at 2-5 years; chronic, with onset in
the first or second decade of life; and late-onset, with the first indication of symptoms in the
2nd-3rd decade of life. Common signs for the first 3 forms are signs of CNS degeneration,
like decreased muscle tone, abnormally increased reflexes, seizures and visual disturbances.
For adult-onset, there may be motor difficulties and some adults may manifest bipolar type
psychological symptoms. Ophthalmologists may be the first to consider TSD by finding a
“cherry red spot” in the macula of the eye, which results from GM2 buildup in the
retinal cells around the central macular area. Diagnosis of TSD is done by determining the
activity of HEX A in serum, leukocytes, tears, or any other body tissue. Genetic testing
for HEX A gene mutations and sequencing of the HEX A gene are used for diagnosis and
heterozygous carrier detection. There is no cure for TSD or its variants.
Treatment for the infantile and juvenile form involves supportive care to manage symptoms.
Usually this involves many specialists including neurologists to manage seizures, gastroenterologists,
surgeons, and nutritionists to manage feeding, as well as occupational and physical therapists
to assist with the tasks of daily living and mobility. Management of symptoms in later
onset forms is also primarily supportive, dealing with the slower, but progressive nature
of the degeneration in these related conditions. Enzyme replacement or gene therapy continue
to be areas of research, but until they are in hand, genetic counselling for individuals
at high risk can help prevent passing on the mutations associated with TSD. More specifically,
couples at risk of having an affected child have options like amniocentesis and chorionic
villus sampling as well as artificial insemination, ovum donation, and in-vitro fertilization
to have children who don’t have Tay-Sachs disease or related GM2 disorders. All right, as a quick recap, Tay-Sachs disease
is a lysosomal storage disease that results in a buildup of GM2 ganglioside in neurons
of the central nervous system. This results in seizures, motor delay, low muscle tone,
and rapid degeneration of the nervous system. Diagnosis is achieved through enzyme assays
and DNA sequencing. There is no cure for Tay-Sachs disease, and treatment involves supportive
therapy. Reproductive counseling, however, is available.

8 Replies to “Tay-Sachs disease – causes, symptoms, diagnosis, treatment, pathology”

  1. Currently making a paper about this disease for my biochem class and wanted to understand more about it. Always on time, Osmosis! Thanks for this!

  2. I always forgot to read up on Tay-Sachs disease ever since it was mentioned by Danny in a Game Grumps episode almost 5 years ago, about how some diseases only affect certain populations of people and how he was confused and interested in the idea that only groups of people got certain diseases–in this case, he used Tay-Sachs disease and the Jewish population as an example.

    Now, though, I completely understand what was going on. It wasn't that Tay-Sachs disease only affects one group of people but that a group of people who build up two chromosone 15s with that gene will have the disease which typically happens in some Jewish groups due to how they prefer to marry and wish to build families.

    You just answered a long-standing question I had lol Thanks a bundle Osmosis <3

  3. Sad for the little ones…Sadder for the parents who have to watch a child die of these diseases. But yes, as we have testing now….get the word out. Good video.

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