What are the recent advances in Ataxia-Telangiectasia (A-T)?

From the Guidelines

Recent advances in ataxia telangiectasia (AT) have focused on improving understanding and management of this rare neurodegenerative disorder, with a strong emphasis on multidisciplinary care protocols addressing immunological, neurological, and pulmonary complications, as outlined in the European Respiratory Review 1. The management of AT patients requires a comprehensive approach, including routine immunological investigations, administration of all available immunizations, and aggressive treatment of respiratory infections, as recommended by the European Respiratory Society 1. Key aspects of care include:

• Immunological management: routine immunological investigations, including total Ig levels and subclasses, specific IgG antibodies, and immunophenotyping of peripheral blood 1
• Respiratory management: aggressive treatment of respiratory infections, use of prophylactic antibiotics, and airway clearance physiotherapy 1
• Cancer screening: annual physical exam, complete blood count, complete metabolic profile, and limited use of ionizing radiation due to increased sensitivity in AT patients 1
• Multidisciplinary care: referrals to neurology, immunology, pulmonology, gastroenterology, and oncology for comprehensive management of AT-related complications 1 The use of antioxidants like N-acetylcysteine (NAC) and EPI-743, as well as glucocorticoid therapy and HDAC inhibitors, may help reduce oxidative stress and improve neurological symptoms in some patients, although more research is needed to confirm their efficacy [@Example@]. Overall, the management of AT requires a coordinated approach, taking into account the patient's individual needs and the latest advances in our understanding of the disease, as highlighted in the European Respiratory Review 1 and Clinical Cancer Research 1.

From the Research

Recent Advances in Ataxia Telangiectasia

• Ataxia telangiectasia (A-T) is a rare, neurodegenerative, and multisystem disease characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure, and an increased risk of malignancies 2.
• The disease is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated) gene, which encodes a protein that coordinates cellular signaling pathways in response to DNA double-strand breaks, oxidative stress, and other genotoxic stress 3.
• A-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages, making diagnosis and management challenging 3, 4.

Clinical Manifestations and Diagnosis

• 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: telangiectasia, frequent sinopulmonary infections, and specific laboratory abnormalities (e.g., IgA deficiency, lymphopenia, and increased alpha-fetoprotein levels) 3.
• 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 3.
• Antenatal diagnosis can be performed if the pathological ATM mutations in that family have been identified in an affected child 3.

Management and Treatment

• 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 3, 4.
• However, other manifestations of A-T, such as immunodeficiency, pulmonary disease, failure to thrive, and diabetes, can be treated effectively 3, 4.
• Current clinical trials represent progress and hope towards disease-modifying therapies for A-T 4.

Prognosis and Quality of Life

• Deterioration of neurologic function with age is associated with dysphagia, aspiration, growth faltering, loss of ambulation, and decline in pulmonary function, morbidities that contribute to shortened life expectancy and decreased quality of life 4.
• Premature death is often due to malignancies or chronic respiratory insufficiency 4.
• A-T is currently managed with supportive care and symptomatic treatment, but a better understanding of the disease's pathogenesis and clinical manifestations can help improve management and treatment in the future 5.