Ataxia telangiectasia

Andreea Nissenkorn, Bruria Ben-Zeev

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Ataxia telangiectasia (AT) is an autosomal recessive multisystem genetic disorder caused by a mutation in the ATM gene encoding for the ATM protein. AT systemic manifestations include cutaneous telangiectasias, radiosensitivity, immune deficiency with recurrent sinopulmonary infections, and a tendency to develop lymphoid malignancies. These complications are explained by the major role played by ATM in DNA repair. AT is also the second most common childhood onset neurodegenerative disorder of the cerebellum, presenting with progressive ataxia and oculomotor apraxia and often accompanied by extrapyramidal movement disorders. Ataxia typically begins around the time children start to walk at about 1 year of age and leads to wheelchair dependence by the second decade of life. Cerebellar atrophy is evident on imaging after 2 years of life and is progressive. Abnormal DNA repair mechanisms do not entirely explain the pathophysiology in nondividing neurons. The nervous system involvement is better explained by the role ATM plays in antioxidative defense, mitochondrial homeostasis, and DNA chromatin packing. A better understanding of the underlying pathophysiologic mechanisms of this devastating disease may enable disease-modifying treatments in the future. Meanwhile, treatment is mainly supportive and does not change the poor prognosis of the disease although it improves the patient's quality of life.

Original languageEnglish
Title of host publicationHandbook of Clinical Neurology
PublisherElsevier B.V.
Pages199-214
Number of pages16
DOIs
StatePublished - 2015

Publication series

NameHandbook of Clinical Neurology
Volume132
ISSN (Print)0072-9752
ISSN (Electronic)2212-4152

Keywords

  • ATM
  • Cerebellar
  • DNA repair
  • Movement disorder
  • Neurodegeneration

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