Neurodegeneration in Ataxia Telangiectasia: What Is New? What Is Evident?

Abstract

This article summarizes evident and recent findings on the characteristics of the neurological phenotype in ataxia telangiectasia (AT), reviews neuropathological and neuroradiological findings, and outlines therapeutic treatment options. In addition, this review offers an overview of current hypotheses on mechanisms of neurodegeneration in AT and discusses their relevance in clinical neurology. The obvious features of neurodegeneration in AT-cerebellar ataxia and dysarthia-are accompanied by a variety of further disabling disease symptoms. Review of the literature outlines a complex pattern of central nervous degeneration in AT that might have been underestimated so far. Neurodegeneration in AT is closely related to the absence or partial lack of the ataxia telangiectasia-mutated (ATM) kinase. ATM is a central player in maintaining cellular homeostasis. Systemic review of the literature reveals a subset of cellular targets hypothesized to count responsible for degeneration in ATM-deficient neurons. Further systematic cliniconeurological, pathoanatomical, and neuroradiological studies are required to understand the structural basis of this neurodegenerative disease. This better understanding has implications for the treatment of AT patients. Second, biochemical and molecular biological studies aimed at deciphering the pathomechanisms of this progressive disorder are necessary for the development of promising future therapies.

Growth retardation and growth hormone deficiency in patients with Ataxia telangiectasia

“…Low levels of GH at a very young age point to an intrinsic failure directly caused by the ATM gene. While the pathogenic significance of IGF-1 in A-T is difficult to envisage, disrupted IGF-1 neuroprotective signalling may constitute a common stage in the pathological cascade associated with neuronal death (Hoche et al, 2012). Indeed, treatment with IGF-1 has been effective in animal models of ataxia (Schubert et al, 2009;Tolbert & Clark, 2003).…”

A Rare Case of Ataxia Telangiectasia in Malaysia

“…In the early stages of the disease, patients with A-T display a cerebellar motor phenotype, including dysmetria of the extremities and ataxic gait 4 . Ataxia is typically observed during the first year of age.…”

Ataxia-telangiectasia: future prospects

“…This ataxia is already evident in the first years of life, and results in wheelchair dependency for most suffering children by the age of 10 years. Although the cerebellum in A-T patients is most profoundly affected with loss of Purkinje and granule cells, progressive neurodegeneration occurs also in other parts of the central nervous system 36–39. Notably, human diseases with the most similar neuropathology to A-T are caused by genes involved in the repair of diverse types of DNA lesions 40.…”