Ataxia Talengiectasia

1. Ataxia telangiectasia
Farouk Kabbara MED III UOB

2. Ataxia
Ataxia describes a lack of muscle coordination during
voluntary movements, such as walking or picking up
objects.
• Ataxia can affect your movements, your speech, your eye
movements and your ability to swallow.
• Persistent ataxia usually results from damage to your
cerebellum — the part of your brain that controls muscle
coordination.
• Many conditions may cause ataxia, including alcohol
abuse, stroke, tumor, cerebral palsy and multiple sclerosis.

3. Ataxia telangiectasia
• Ataxia telangiectasia (Boder-Sedgwick syndrome or Louis–Bar)
syndrome is a rare, neurodegenerative, inherited disease that
affects many parts of the body and causes severe disability.
Ataxia refers to poor coordination and telangiectasia to small
dilated blood vessels, both of which are hallmarks of the disease.
A child who has inherited A-T will display nervous system
abnormalities by age 2, and will then progressively lose muscle
control.

4. Genetics
Recessive
it will not affect the body
unless it has twin copies
of the recessive genetic
anomaly.
ATM gene
sequence disruption in
the gene ATM (Ataxia
telangiectasia mutated)
Autosomal

5. Function
01
The gene normally repairs
double-stranded DNA
breaks.
Discovery
02
Ataxia-telangiectasia
mutated, discovered in
1995, is on chromosome 11.
Critical role
03
It mobilizes several other
genes try to repair the DNA
damage or destroy the cell
if they can't repair it.
These downstream genes include
tumor suppressor proteins p53
and BRCA1, checkpoint kinase
CHK2, checkpoint proteins RAD17
and RAD9, and DNA repair protein
NBS1.
Pathophysiology

6. ATM gene are thought to come in two types
Null mutations
Complete loss of function
of the protein, and are
therefore inherited in a
recessive manner and
cause A-T.
Missense mutations
Stable, full sized protein
with reduced function.
These mutations act by
dominantly interfering
with the normal copy of
the protein.

7. The symptoms
As symptoms
become
progressively worse,
speech becomes
slurred and difficult.
At first, infants with
A-T appear healthy.
By age 2, however,
parents notice
increased
clumsiness and
balance problems.
By age 10 to 12,
children with A-T
lose muscle control.
Between ages 2 to 8,
the telangiectases -
tiny, red “spider”
veins - appear on the
cheeks, ears, and in
the eyes.

8. Other symptoms
Missing or
abnormally developed
thymus gland
Retarded growth Diabetes
Immune system
deficiencies, low
immunoglobulin
concentrations

9. Other symptoms
Chromosomal instability
Hyper-sensitivity to
ionizing radiation
Absent thymic shadow on
X-ray
Ovarian dysgenesis
Raised alpha-fetoprotein
levels
Telangiectasias of the
eyes and skin

10. Diagnosis
Examination and
identification of both
ataxia and oculo-
telangiectasia or skin
telangiectasia.
Followed by
laboratory tests for
serum AFP level
Response of white
blood cells to X-rays
and measurement of
the level of ATM
protein
Molecular diagnosis of A-T
can be carried out by
sequencing all 66 exon of the
gene or by linkage if there is a
significant family history
01 02
03 04

11. Differential Diagnosis
Other Problems to Be Considered
- Hartnup disease
- Cockayne syndrome
- De Sanctis-Cocchione syndrome
- Friedreich ataxia
- Rendu-Osler-Weber disease

12. Treatment
Treatment is
symptomatic and
supportive.
Antibiotics are used
to treat infections
Gamma-globulin
injections may be given
to help supplement a
weakened immune
system
Physical and
occupational therapy
may help maintain
flexibility.
High-dose vitamin
regimens may also
be used

13. Chemotherapy
Some physicians recommend low doses of
chemotherapy to reduce the risk of cancer but this is
controversial.

14. Prognosis
Those with A-T usually die in
their teens or early 20s
although some individuals
have been known to live to
over 40.
Mortality is mainly due to the
compromised immune
system, which causes
recurrent respiratory
infections, predisposition to
cancer, and a high rate of
pulmonary problems.

15. References
http://www.neuroskills.com/brain.shtml
http://www.mayoclinic.com/health/ataxia/DS00910

16. —Helen Keller
“Although the world is full of
suffering, it is also full of the
overcoming of it”

17. Thanks!
Do you have any questions?
kabbarafarouk@gmail.com