viernes, 24 de febrero de 2017

Ataxia telangiectasia: a review | Orphanet Journal of Rare Diseases | Full Text

Ataxia telangiectasia: a review | Orphanet Journal of Rare Diseases | Full Text

Orphanet Journal of Rare Diseases - IMPACT FACTOR 3.29

Ataxia telangiectasia: a review

  • Cynthia Rothblum-OviattEmail authorView ORCID ID profile,
  • Jennifer Wright,
  • Maureen A. Lefton-Greif,
  • Sharon A. McGrath-Morrow,
  • Thomas O. Crawford and
  • Howard M. Lederman
Orphanet Journal of Rare Diseases201611:159
DOI: 10.1186/s13023-016-0543-7
Received: 18 September 2016
Accepted: 16 November 2016
Published: 25 November 2016


Definition of the disease

Ataxia telangiectasia (A-T) is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome.


The world-wide prevalence of A-T is estimated to be between 1 in 40,000 and 1 in 100,000 live births.

Clinical description

A-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages. Neurological symptoms most often first appear in early childhood when children begin to sit or walk. They have immunological abnormalities including immunoglobulin and antibody deficiencies and lymphopenia. People with A-T have an increased predisposition for cancers, particularly of lymphoid origin. Pulmonary disease and problems with feeding, swallowing and nutrition are common, and there also may be dermatological and endocrine manifestations.


A-T is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated) gene which encodes a protein of the same name. The primary role of the ATM protein is coordination of cellular signaling pathways in response to DNA double strand breaks, oxidative stress and other genotoxic stress.


The diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with one or more of the following which may vary in their appearance: telangiectasia, frequent sinopulmonary infections and specific laboratory abnormalities (e.g. IgA deficiency, lymphopenia especially affecting T lymphocytes and increased alpha-fetoprotein levels). Because certain neurological features may arise later, a diagnosis of A-T should be carefully considered for any ataxic child with an otherwise elusive diagnosis. A diagnosis of A-T can be confirmed by the finding of an absence or deficiency of the ATM protein or its kinase activity in cultured cell lines, and/or identification of the pathological mutations in the ATM gene.

Differential diagnosis

There are several other neurologic and rare disorders that physicians must consider when diagnosing A-T and that can be confused with A-T. Differentiation of these various disorders is often possible with clinical features and selected laboratory tests, including gene sequencing.

Antenatal diagnosis

Antenatal diagnosis can be performed if the pathological ATM mutations in that family have been identified in an affected child. In the absence of identifying mutations, antenatal diagnosis can be made by haplotype analysis if an unambiguous diagnosis of the affected child has been made through clinical and laboratory findings and/or ATM protein analysis.

Genetic counseling

Genetic counseling can help family members of a patient with A-T understand when genetic testing for A-T is feasible, and how the test results should be interpreted.

Management and prognosis

Treatment of the neurologic problems associated with A-T is symptomatic and supportive, as there are no treatments known to slow or stop the neurodegeneration. However, other manifestations of A-T, e.g. immunodeficiency, pulmonary disease, failure to thrive and diabetes can be treated effectively.


Cancer Neurodegeneration Cerebellum Purkinje cells Immunodeficiency Dysphagia Pulmonary disease

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