1. ATAXIA TALANGIECTASIA
CASE 1

2. 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.

3. 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.

5. 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

8. 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

9. 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

10. 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

11. 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