In this issue, Dr Marius Theis and colleagues from Goethe University, Frankfurt, characterize the clinical and electrophysiological age-related features of the peripheral polyneuropathy in 42 patients with classical ataxia-telangiectasia (A-T) aged 1–28 years old [1].
Ataxia-telangiectasia is a rare autosomal recessive progressive and life-shortening multisystem disease due to mutations in the ataxia-telangiectasia mutated gene (ATM). This codes for a key serine/threonine protein kinase involved in DNA repair and a host of other nuclear, cytoplasmic and mitochondrial functions [2]. Clinically the progressive polyneuropathy is overshadowed by ever more florid and disabling cerebellar ataxia, dystonia and movement disorders, affecting fine and gross motor function, eye movements, speech and swallowing, from early childhood. In addition to the neurodegenerative features, patients develop immune deficiency, cancer susceptibility and chronic lung disease reminiscent of cystic fibrosis [3]. Most people with classical A-T and no kinase function die before they reach 30 years of age, although a mild variant A-T, usually with residual kinase function, is increasingly being recognized [4].
Until now the peripheral neuropathy was not well described, but this careful cross-sectional prospective study included a detailed history of neuropathic symptoms, a clinical examination for neuropathic signs in the extremities, as well as non-invasive nerve conduction studies of both median and tibial motor and sensory amplitudes and velocities.
As expected, symptoms, signs and neurophysiological abnormalities progressed with age, but what was not expected was that neurophysiological abnormalities could be picked up long before symptoms and signs, even within the first 2 years of life, that is, before some children will have been diagnosed. The progressive motor neuropathy in both upper and lower limbs was mainly denervating early on, becoming mainly mixed axonal and denervating with age. The progressive sensory neuropathy was often axonal early on, becoming mixed axonal and denervating with age.
This highlights the potential for non-invasive nerve conduction studies to be used as a biomarker in future clinical trials in people with A-T of all ages, although it remains to be seen if improvements in neurophysiological indices can be achieved
