Transcript ATAXIA TALANGIECTASIA DOLLY EWILI

ATAXIA
TALANGIECTASIA
CASE 1
• A 7 year old child was brought to the OPD for
dilated and tortuous blood vessels in the clear of
the eyes. Medical examination revealed
cerebellar ataxia and bilateral ocular
telangiectasia. Two years later he developed
malignant lymphoma and died of respiratory
failure.
• What is the molecular basis of this disease?
• Describe the function of the gene responsible for
this disorder.
Ataxia telangiectasia (A-T) (also referred to
as Louis–Bar syndrome) is a rare,
neurodegenerative, inherited disease causing
severe disability. Ataxia refers to poor
coordination and telangiectasia to small dilated
blood vessels, both of which are hallmarks of the
disease.
A-T is an autosomal recessive disease caused by
inactivating mutations of the ATM gene
(11q22.3).
There is no cure for A-T and, currently, no way to
slow the progression of the disease. Treatment is
symptomatic and supportive.
ATM GENE
The ATM gene provides instructions for making a protein that
helps control cell division and is involved in DNA repair. This
protein plays an important role in the normal development
and activity of several body systems, including the nervous
system and immune system. The ATM protein assists cells
in recognizing damaged or broken DNA strands and
coordinates DNA repair by activating enzymes that fix the
broken strands. Efficient repair of damaged DNA strands
helps maintain the stability of the cell's genetic
information.
With a break in double stranded DNA, ATM interacts with
many proteins to stop cell cycle, induce DNA repair and
apoptosis. Allows cell to repair DNA before continuing
division.
Irradiation and radiomimetic compounds induce DSBs
Symptoms
Symptoms often appear in early childhood. They
include:
• Bronchiestasis
• Sinus
• Cutaneomucosal talangectasia
• Difficulty with movement and co-ordination
• Predisposition to infection
• Increased risk of cancer
• Slurred speech
• Oculomotor apraxia
• athetoid movements
DIAGNOSIS
Can be made by:
Elevated alpha fetal proteins (a protein that is
high in children with A-T because of their lack
of ATM protein)
Absent ATM genes in WBC
Increased sensitivity to xray
Chromosomal instability (broken)
Cerebellar atrophy on MRI scan
DIFFERENTIAL DIAGNOSIS
Cerebellar ataxia, a condition that affects
balance and co-ordination but isn’t
progressive.
Friedreich ataxia, a trinucleotide repeat,
mutation in frataxin gene, Romberg sign. But
no talangiectasia, no oculomotor apraxia and
a normal alpha fetoprotein.
Cogan’s oculomotor apraxia which occurs in
early childhood and improves with time unlike
A-T
TREATMENT
The therapy for AT is supportive and includes
administration of antibiotics for infection,
physiotherapy for pulmonary bronchiectasis,
physical therapy to prevent contractures in
patients with neurologic dysfunction,
Antibiotics to boost the immune system