Ataxia- Telangiectasia

What is Ataxia-Telangiectasia
Rare autosomal recessive genetic disorder of
childhood that results from defective nuclear
DNA repair mechanisms

AT is a multisystemic disease characterized by

progressive cerebellar ataxia, choreoathetosis,
oculocutaneous telangiectasias, frequent
infections, increased sensitivity to ionizing
radiation, and predisposition to malignancies
 What Causes A-T?
A mutated gene called ATM produces a
mutated ATM protein (ataxia
telangiectasia mutated)

Found by genetic linkage analysis

Gene in genomic location: bands according to Ensembl, locations
according to GeneLoc (and/or LocusLink and/or Ensembl if
different)
Apparently results from the coexistence of
a T cell deficiency with a defect in DNA
repair, which leads to extreme, nonrandom
chromosomal instability. The sites of
chromosomal breakage involve
Chromosome 7 and 14.
Immunologic Manifestations:
The thymus is hypoplastic or dysplastic
and the thymus-dependent zones of the
lymph nodes are void of cells.
Serum levels of IgA, IgE, and IgG2 are
decreased while IgM, IgG1, and IgG3 fall
within normal ranges.
The signs and symptoms of the
disease appear to result from a concomitant
T cell deficiency, deficiency of DNA repair,
and disordered IgG synthesis.
SIGNS AND SYMPTOMS
Cerebellar Ataxia
Ocular Telangiectasia

www.indianpediatrics.net/ dec-99/99-dec-29.htm
 Slurred speech (noted after age 5 to 8),
ocular apraxia

Choreoathetosis

Elevated serum α-fetoprotein (>10 ng/ml)

Hypersensitivity to radiotherapy
 Frequent sinopulmonary infections
secondary to immunodeficiency

Increased risk for malignancy

especially leukemia and T cell lymphoma

Dysarthria, severe twitching, decreased

deep tendon reflexes, motor retardati
 TREATMENT
No proven disease-specific treatment is
currently available.

Treatment is focused on amelioration of

disease manifestation.

Gene Therapy
 Surveillance for infections and
neoplasms is necessary. Individuals with
frequent and severe infections may benefit
from intravenous immunoglobulin. Children
should be immunized with pneumococcal
and influenza vaccines.
Nonpharmacologic Therapy
 Minimize radiation as it may induce
further chromosomal damage and lead to
neoplasms.
 Physical and occupational therapy to
maintain flexibility and minimize
contractures.

Complementary and Alternative Medicine

 Antioxidant treatment with Vitamin E
Laboratory Diagnosis:
Serum immunoglobulin (IgA, IgG
subclasses and IgE) should be measured to
evaluate for immunoglobulin deficiency and
oligoclonal gammopathy.
Test for Serum α-fetoprotein
Prenatal Testing
Immunoblotting
Imaging studies – shows cerebellar
atrophy.
THE END