Abstract

Ataxia telangiectasia (AT) is a multisystem autosomal recessive disorder caused by mutations in the ATM gene found on the large arm of chromosome 11 (11q 22–23). The ATM gene encodes the protein kinase ATM, which is the key regulator of cellular response to breaks in double stranded DNA. As a result patients with AT show an increased sensitivity to ionising radiation with increased predisposition to cancer. Approximately 10% of AT homozygotes develop cancer, mostly of the lymphoid system. The immunodeficiency seen in AT is variable and usually manifests as decreased or absent immunoglobulins making patients more susceptible to infections. Laboratory findings show elevated alphafetoprotein (AFP), cerebellar atrophy on MRI as well as mutations in the ATM gene. AT shows clinical heterogeneity. In classical AT, the most obvious and disabling characteristic is the progressive cerebellar ataxia and occulomotor apraxia. Presentation is usually by the age of two years and patients are often wheelchair bound by their early teens. As well as the progressing ataxia, patients may have chorea and dystonia. Patients with AT have reduced lifespan. The incidence is about 3 per 100,000.

We report a case of a 60 year old woman who was referred to the Sheffield Ataxia Clinic with progressive gait deterioration over a period of eight years. She was still able to walk with walking aids. She had a rather vague childhood history of choreoathetosis but remained mobile and stable without significant gait difficulties until she was 52 years of age.

On examination she was found to have cerebellar signs including gaze evoked nystagmus, limb ataxia, dysarthria and intention tremor. There was no evidence of occulomotor apraxia. She had evidence of telangiectasia on her face. She had never suffered from frequent infections and there was no history of cancer in her or her family. MRI showed cerebellar atrophy and alpha fetoprotein levels were within the upper limit of normal at 15 KU/L (range 0–15 KU/L). She had slightly low immunoglobulins of the IgG and IgM class.

Genetic testing revealed compound heterozygosity for hypomorphic ATM mutations resulting in some residual ATM protein levels. Milder forms of Ataxia telangiectasia have very rarely been reported and are often referred to as A–T variants. Such cases are characterised by one or more of the following: later age of onset, slow progression and an extended life span compared to patients with classical A–T. Chromosomal instability and cellular radio sensitivity are much less prominent which means that they are not susceptible to recurrent infections and increased incidence of cancer. This case illustrates the importance of considering AT as the cause of ataxia even in patients with late onset ataxia.