Tay Sachs disease is a fatal genetic disorder that results in the progressive destruction of the nervous system in children. It is caused by the absence of the enzyme hexosaminidase A, which leads to the abnormal accumulation of a fatty substance called GM2 ganglioside in nerve cells, especially in the brain. This causes cell damage and death. There is currently no treatment for Tay Sachs disease, which is usually fatal by age 4. The disease is inherited in an autosomal recessive pattern and has a high incidence among Ashkenazi Jews, French Canadians, and Cajuns.

1. Tay Sachs Disease
By: Mohamed Samir El-Asaly
PT, CKTP
2016

2. What is Tay-Sachs?
• Tay-Sachs diseases causes a progressive
deterioration of nerve cells and of mental
and physical abilities that begins around six
months of age.
• The disease occurs when harmful quantities
of cell membrane components components
known as gangliosides accumulate in the
brain’s nerve cells

3. What is Tay-Sachs?
• A fatal genetic disorder
• Most commonly occurring in
children
• Results in progressive
destruction of the nervous
system
• Caused by the absence of a vital
enzyme called hexosaminidase-
A (Hex-A).

5. What is Tay-Sachs?

6. Without
Hex- A
A fatty
substance
GM2
gangloside
accumulate
abnormally
in the cell
Especially
in nerve
cells of the
brain
Cell
damage
and death

7. What is Tay-Sachs?
•Autosomal recessive lipid storage
disorder
•High incidence among Ashkanazi Jews,
Cajuns, French Canadians
•Lack of enzyme, Hexosaminidase A
•Leads to accumulation of GM2
ganglioside in the neurons

8. How do people inherit Tay-Sachs
disease?
• This condition is inherited in an autosomal
recessive pattern, which means both copies of
the gene in each cell have mutations
(Incomplete dominance)
• The parents of an individual with an autosomal
recessive condition each carry one copy of the
mutated gene, but they typically do not show
signs and symptoms of the condition.

11. Symptoms of Tay-Sachs
• Infants initially appear healthy; symptoms
appear not before 6 months of age
• Development begins to slow
• Loss of motor skills, mental functions
• Child becomes blind, deaf, paralyzed, mentally
retarded, and non-responsive
• Fatal, usually by age 4

12. Classical Diagnosis
• Appearance of
aforementioned
symptoms
• “Cherry-red” spot on
eyes, caused by lipid-
laden ganglion cells
• Larger startle reflex to
noise
• Before 1970, Tay-Sachs
could not be diagnosed at
birth

13. Classical Testing
• In 1969, researchers discovered the
biochemical basis for the disease
• Michael Kaback of JHU created an
enzyme assay to test for heterozygotes
• Detects individuals with lower levels of
Hex-A
• Can detect all mutations, but with
some inconclusive results

14. Classical Treatment
• There is currently no treatment for Tay-
Sachs disease
• Supportive treatment
• Anti-seizure medicine
• Feeding tube
• Proper nutrition, hydration

15. Genetic Testing
• Caused by mutations in both
alleles of HEXA gene on
chromosome 15. Exact location
(15q23- q24) determined in
1990.
• PCR tests for actual mutations.
Gives definite results, but only
for known mutants.

16. Treatment
All in experimental stages
• Gene therapy
1. Replace defective HEXA genes.
2. Difficult to transport genes to neurons.
• Enzyme replacement therapy by replacing Hex-A.
1. Hex-A is too big to pass through the blood- brain
barrier.
2. Neurons are unable to take up Hex-A because it is too
big.

17. Prevention
• Prenatal diagnosis
• Genetic testing by amniocentesis
• Embryo screening: Test embryo prior to in
vitro fertilization
Select embryos without Tay-Sachs

18. Thank you for Listening