Ataxia-telangiectasia
Ataxia-telangiectasia is an autosomal recessive disorder of the ATM DNA-repair gene, producing a triad of progressive cerebellar ataxia, oculocutaneous telangiectasias, and IgA-predominant immunodeficiency, along with markedly increased radiosensitivity and a substantial lifetime risk of lymphoma or leukemia. Diagnosis rests on the clinical triad plus elevated alpha-fetoprotein and low IgA, confirmed by ATM genetic testing; treatment is supportive, centered on infection prevention and minimizing ionizing radiation.
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What this article covers
- Overview
Definition: ataxia-telangiectasia is an autosomal recessive disorder caused by mutation of the ATM (ataxia-telangiectasia mutated) gene, whose encoded kinase normally detects DNA double-strand breaks…
- Epidemiology
Rare autosomal recessive disorder: ataxia-telangiectasia is an uncommon inherited ataxia of childhood.
- Risk factors
Biallelic ATM mutation: the disorder requires inheritance of one mutated ATM allele from each parent, who are typically unaffected carriers.
- Pathophysiology
Loss of ATM-mediated DNA damage detection: the ATM kinase normally senses double-strand DNA breaks and halts cell-cycle progression so repair can occur; without it, damage goes undetected, the cell…
- Clinical features
Cerebellar ataxia, usually the first presenting symptom: typically appears in infancy or early childhood, often as unsteady gait once independent walking begins, and progresses over subsequent years.
- Differential diagnosis
Friedreich ataxia: also presents with progressive gait ataxia in childhood but reflects a GAA trinucleotide repeat expansion in the frataxin gene rather than ATM, and is distinguished by the presence…
- Diagnosis
Diagnosis rests on the clinical triad of cerebellar ataxia, oculocutaneous telangiectasias, and IgA-predominant immunodeficiency, confirmed by genetic testing identifying biallelic pathogenic ATM variants.
- Management
First, confirm the diagnosis and set up multidisciplinary care: coordinate neurology, immunology, pulmonology, and oncology surveillance from diagnosis, since there is no treatment that reverses the…
- Complications
Chronic lung disease: recurrent sinopulmonary infection, worsened by impaired airway clearance as bulbar and motor function decline, leads to interstitial lung disease and is a leading cause of morbidity and mortality.
- Prognosis
Progressive, life-limiting disease: ataxia-telangiectasia is a progressive multisystem disorder; ambulation typically declines over childhood and adolescence.
- Prevention
No primary prevention of the genetic defect exists, since the disorder results from inherited biallelic ATM mutations rather than a modifiable exposure.
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Related articles
- Friedreich ataxia
Friedreich ataxia is an autosomal recessive trinucleotide (GAA) repeat disorder that silences the frataxin gene, causing mitochondrial iron accumulation and degeneration of the spinocerebellar and dorsal column tracts. It presents in childhood or adolescence with progressive gait ataxia, dysarthria, and loss of deep tendon reflexes, and its leading cause of death is hypertrophic cardiomyopathy. Diagnosis is by genetic testing; management is multidisciplinary and supportive.
- Selective IgA deficiency
Selective IgA deficiency is the most common primary antibody deficiency, defined by a serum IgA level below 7 mg/dL with normal IgG and IgM. Most patients are asymptomatic; management is supportive, treating sinopulmonary and gastrointestinal infections as they occur and using washed or IgA-deficient blood products to prevent anaphylactic transfusion reactions.