Clinical, biological and genetic study of 24 patients with ataxia telangiectasia from southern Tunisia.

Ataxia telangiectasia is a multisystem disease with an autosomal recessive inheritance. It is characterized by progressive cerebellar ataxia, oculocut aneous telangiectasia, humoral and cellular immunodeficiencies and high inc idence of neoplasia and radiosensitivity, A 5 year retrospective survey inc luded 24 patients belonging to 17 families. Cerebellar ataxia was the first clinical symptom and was usually noticed when the child began to walk. Mea n age of onset was 2.9+/-1.8 years. Oculocutaneous telangiectasia was prese nt in 17 cases and appeared between 2 and 8 years and then spread in a char acteristic symmetrical pattern. When ocular telangiectasia was absent (6 ca ses), the diagnostic of ataxia telangiectasia was retained on oculomotor ap raxia (2 cases), recurrent sinopulmonary infections (3 cases) and/or a sib with typical ataxia telangiectasia (1 case). Recurrent sinopulmonoray infec tions, absence or low serum level of IgA (78 p.100) and lymphopenia reveale d immunodeficiency. Among 12 patients, chromosomal instability was observed in 5. Balanced rearrangements involving chromosomes 2, 7, 14, 22, 1, 3 and 11. The responsible gene, ATM, encodes a large protein kinase with a phosp hatidylinonositol 3-kinase-like domain. Ataxia telangiectasia patients have a 100 fold higher risk of cancer than the general population. We reported, in the same family two patients who developed neoplasia, (lymphoma and leu kemia). During follow-up, a progressive worsening was observed in ail cases . Three patients have died.