Ataxia Telangiectasia (A-T) is a multisystemic autosomal recessive disorder affecting between 1:40,000 and 1:200,000 individuals world-wide. The cardinal features of the disease are ataxia, due to loss of the cerebellar Purkinje cells and causing unsteady gait, involuntary movements, slurred speech, and difficulty in controlling eye movements; telangiectasias (dilated blood vessels) on the conjunctivas and skin; radiosensitivity, both at systemic and cellular level; and elevated serum  alpha-fetoprotein.

The onset of cerebellar ataxia is generally in the first year of life; other neurological features appearing with the age are oculomotor apraxia, choreoatethosis, nystagmus, strabismus, dyslalia, hypotonia and in some cases epilepsia. As the disease progresses, the individual’s immune system weakens, leading to recurrent respiratory infections and predisposition to cancer, expecially to leukemia and lymphomas.

People with AT usually die in their teens or early twenties. The clinical diagnosis of AT can be difficult before the appearance of telangiectasias. The discovery of the ATM gene that, when mutated, causes the disease, has opened the way to a more accurate diagnosis. The typical A-T phenotype is caused by biallelic ATM mutations that truncate or severely destabilize the gene product.

Occasionally milder cases of the disease, showing later age of onset or moderate severity of clinical features, longer life-span and intermediate cellular radiosensitivity (the so-called ‘A-T variants’) have been reported. The recent molecular discoveries allowed us to classify most of these variant patients as Ataxia Telangiectasia-Like Disorder (AT-LD), Ataxia with Oculomotor Apraxia type 1 (AOA1) and Ataxia with Oculomotor Apraxia type 2 (AOA2).

The ATM gene occupies 150 kb of genomic DNA and is structured in 66 exons that encode a 13kb transcript, the ATM protein. ATM is a phosphoprotein belonging to the family of the PI3-kinase proteins and is involved in the cellular responses to DNA damage (specifically to DNA double strand breaks) and in the regulation of cell cycle progression. A-T patients lack the ATM protein due to the nature of the mutations, generally resulting in the truncation of the coding. Some of them, having residual ATM protein level (5% to 20%), seem to present with a later onset and a slower neurological progression.  

This website is reserved to scientist working in the A-T field, who could use it to insert the patients’ data and to discuss between them the obtained results.