Ataxia-Telangiectasia (A-T) is a rare, progressive genetic disorder affecting multiple body systems. It causes a decline in neurological function, immune system issues, and an increased risk of certain cancers.
What is Ataxia-Telangiectasia
A-T is a neurodegenerative disorder primarily affecting movement and coordination. It causes progressive neurological impairment, particularly impacting the cerebellum. The condition also has multisystemic effects.
The immune system is significantly compromised, leading to heightened susceptibility to infections. Skin and blood vessels are also affected, with characteristic visible signs. Neurological symptoms worsen over time, often leading to increasing reliance on mobility aids.
Common Manifestations
Signs and symptoms of A-T typically begin in early childhood, around 1 to 2 years of age, with progressive walking difficulties and balance issues. A primary neurological symptom is ataxia, characterized by poor coordination and an unsteady gait. Children with A-T may sway or stagger when walking and struggle with stability, even when sitting or standing still. This lack of coordination is linked to cerebellar abnormalities.
Other neurological manifestations include dysarthria, which is slurred speech, and oculomotor apraxia, causing difficulty coordinating head and eye movements. As the condition progresses, involuntary movements like choreoathetosis (jerky and writhing motions) can appear, often around 9-10 years of age, and tend to worsen.
A distinct physical hallmark of A-T is telangiectasias, small, widened blood vessels appearing as reddish or purple clusters. These dilated capillaries are commonly seen on the white part of the eyes (sclera), making them appear bloodshot. They may also appear on sun-exposed skin, such as the ears and skin folds, usually becoming noticeable around 3 to 6 years of age.
Immune system deficiencies affect B and T cells in 60-80% of individuals with A-T, leading to increased susceptibility to recurrent infections, particularly those affecting the ears, sinuses, and lungs. There is an elevated risk of certain cancers, predominantly lymphoid neoplasms like lymphoma and leukemia, with about 35% of patients developing cancer by age 20. Other potential issues include growth delays and, in some cases, glucose intolerance.
Genetic Origin and Diagnosis
Ataxia-Telangiectasia is caused by alterations in the ATM gene (Ataxia-Telangiectasia Mutated), located on chromosome 11q22.3. This gene plays a significant role in DNA repair, specifically in responding to DNA double-strand breaks. Mutations in the ATM gene often lead to a nonfunctional or truncated protein, disrupting this repair process.
The inheritance pattern for A-T is autosomal recessive. An individual must inherit two altered copies of the ATM gene, one from each parent, to develop the condition. Parents are typically carriers, possessing one normal and one altered copy of the ATM gene without exhibiting symptoms.
Diagnosis of A-T often begins with clinical suspicion. Confirmation is primarily achieved through genetic testing, which identifies specific ATM gene mutations. Other supportive laboratory tests include elevated alpha-fetoprotein, a protein normally found in higher concentrations during fetal development, and low levels of immunoglobulins, which are antibodies involved in immune response.
Approaches to Management
There is no cure for Ataxia-Telangiectasia. Management focuses on supportive care and addressing symptoms to improve quality of life.
Neurological management involves a multidisciplinary approach to maintain functional abilities. Physical therapy helps manage ataxia by improving balance and coordination. Occupational therapy assists with daily living activities affected by motor challenges, and speech therapy addresses dysarthria to aid communication.
Immunological management is a significant aspect of care due to the weakened immune system. Immunoglobulin replacement therapy (IVIG or SCIG) can prevent recurrent infections by supplementing antibody levels. Prompt antibiotic treatment is used for acute infections to prevent severe complications.
Due to increased cancer risk, regular cancer surveillance is important, involving routine screenings for early detection of malignancies like lymphoma and leukemia. Skin care, including sun protection, is recommended due to telangiectasias, especially in sun-exposed areas.
A multidisciplinary care team, including neurologists, immunologists, oncologists, and various therapists, coordinates care for individuals with A-T. Research efforts are ongoing to explore potential new therapies, such as gene therapy and other pharmacological interventions, with some showing promising preliminary results.