Ataxia Telangiectasia (AT) is a rare and progressive genetic disorder characterized by primary immunodeficiency and a resultant degradation of the nervous system. The condition manifests itself in childhood, usually within the first decade of life. Initial symptoms include delayed development of motor skills, poor balance and hand co-ordination, chorea, muscle twitches, oculomotor apraxia, and slurred speech. Most children have a weakened immune system, making them susceptible to recurrent infections, most commonly, bronchitis and sinusitis. Telangiectasias, or small, red spider veins, may appear later on the ears, cheeks, or in the corners of the eye. Most children become wheelchair-bound by their teens. Patients have a higher chance of developing cancers, especially acute lymphocytic leukemia or lymphomas.
Mutations in the ATM (Ataxia-Telangiectasia Mutated) gene are responsible for causing AT. Under normal circumstances, this gene codes for a protein kinase that performs two related functions: cell division control and DNA repair in conjunction with the p53 protein. Mutant forms of this gene result in non-functional protein, which cause cellular death, especially in the cerebellum. This leads to the characteristic ataxic symptoms of the condition. In addition, mutant proteins are not able to perform their function of DNA repair, causing defective cells to multiply uncontrollably, resulting in cancers.
By linkage studies in a Jewish-Moroccan family with AT of the group C type, Ziv et al. (1991) found that the ATC (A-T complementation group C) gene localizes to the same region (11q22-q23) as found in group A families.
Osundwa and Dawod (1994) described a 4-year old Palestinian girl in Qatar, who presented with a 2 year history of difficulty in walking. She was born to consanguineous parents and had a normal neonatal period. She walked at 12-months of age and had delayed speech. She also showed a history of six to nine episodes of upper respiratory infections each year. Upon examination, she was found to have telangiectasia on her conjunctiva and pinna. She was dysarthric, had an abnormal gait and bilateral limb ataxia. Her blood count was normal, but her alpha fetoprotein levels were elevated, while serum IgA and IgE levels were reduced (normal IgG and IgM). She also had elevated CD8 subpopulation (68%). She was diagnosed with ataxia telangiectasia. Interestingly, her younger sister was diagnosed with common variable immunodeficiency, prompting Osundwa and Dawod (1994) to suggest a common etiology for both immune system defects. Two other brothers were normal.
[See: Palestine > Osundwa and Dawod, 1994]