Ataxia telangiectasia (A-T) (also referred to as LouisBar syndrome) is a rare, neurodegenerative, inherited disease causing severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease.[1]

A-T affects many parts of the body:

Symptoms most often first appear in early childhood (the toddler stage) when children begin to walk. Though they usually start walking at a normal age, they wobble or sway when walking, standing still or sitting, and may appear almost as if they are drunk. In late pre-school and early school age they develop difficulty moving the eyes in a natural manner from one place to the next (oculomotor apraxia). They develop slurred or distorted speech, and swallowing problems. Some have an increased number of respiratory tract infections (ear infections, sinusitis, bronchitis, and pneumonia). Because not all children develop in the same manner or at the same rate, it may be some years before A-T is properly diagnosed. Most children with A-T have stable neurologic symptoms for the first 45 years of life, but begin to show increasing problems in early school years.

A-T is caused by a defect in the ATM gene,[2] which is responsible for managing the cells response to multiple forms of stress including double-strand breaks in DNA. In simple terms, the protein produced by the ATM gene recognizes that there is a break in DNA, recruits other proteins to fix the break, and stops the cell from making new DNA until the repair is complete.[3]

There is substantial variability in the severity of features of A-T between affected individuals, and at different ages. The following symptoms or problems are either common or important features of A-T:

Many children are initially misdiagnosed as having ataxic cerebral palsy. The diagnosis of A-T may not be made until the preschool years when the neurologic symptoms of impaired gait, hand coordination, speech and eye movement appear or worsen, and the telangiectasia first appear. Because A-T is so rare, doctors may not be familiar with the symptoms, or methods of making a diagnosis. The late appearance of telangiectasia may be a barrier to the diagnosis. It may take some time before doctors consider A-T as a possibility because of the early stability of symptoms and signs.

The first indications of A-T usually occur during the toddler years.[4][5] Children start walking at a normal age, but may not improve much from their initial wobbly gait. Sometimes they have problems standing or sitting still and tend to sway backward or from side to side. In primary school years walking becomes more difficult, and children will use doorways and walls for support. Children with A-T often appear better when running or walking quickly in comparison to when they are walking slowly or standing in one place. Around the beginning of their second decade children with typical forms of A-T start using a wheelchair for long distances. During school years children may have increasing difficulty with reading because of impaired coordinating of eye movement. At the same time other problems with fine motor functions (writing, coloring, and using utensils to eat), and with slurring of speech (dysarthria) may arise. Most of these neurologic problems stop progressing after the age of about 12 15 years, though involuntary movements may start at any age and may worsen over time. These extra movements can take many forms, including small jerks of the hands and feet that look like fidgeting (chorea), slower twisting movements of the upper body (athetosis), adoption of stiff and twisted postures (dystonia), occasional uncontrolled jerks (myoclonic jerks), and various rhythmic and non-rhythmic movements with attempts at coordinated action (tremors).

Prominent blood vessels (telangiectasia) over the white (sclera) of the eyes usually occur by the age of 58 years, but sometimes later or not at all.[6] The absence of telangiectasia does not exclude the diagnosis of A-T. Potentially a cosmetic problem, the ocular telangiectasia do not bleed or itch, though they are sometimes misdiagnosed as chronic conjunctivitis. It is their constant nature, not changing with time, weather or emotion, that marks them as different from other visible blood vessels. Telangiectasia can also appear on sun-exposed areas of skin, especially the face and ears. They occur in the bladder as a late complication of chemotherapy with cyclophosphamide, have been seen deep inside the brain of older people with A-T, and occasionally arise in the liver and lungs.

About two-thirds of people with A-T have abnormalities of the immune system.[7] The most common abnormalities are low levels of one or more classes of immunoglobulins (IgG, IgA, IgM or IgG subclasses), not making antibodies in response to vaccines or infections, and having low numbers of lymphocytes (especially T-lymphocytes) in the blood. Some people have frequent infections of the upper (colds, sinus and ear infections) and lower (bronchitis and pneumonia) respiratory tract. All children with A-T should have their immune systems evaluated to detect those with severe problems that require treatment to minimize the number or severity of infections. Some people with A-T need additional immunizations (especially with pneumonia and influenza vaccines), antibiotics to provide protection (prophylaxis) from infections, and/or infusions of immunoglobulins (gamma globulin). The need for these treatments should be determined by an expert in the field of immunodeficiency or infectious diseases.

People with A-T have a highly increased incidence (approximately 25% lifetime risk) of cancers, particularly lymphomas and leukemia, but other cancers can occur.[8] When possible, treatment should avoid the use of radiation therapy and chemotherapy drugs that work in a way that is similar to radiation therapy (radiomimetic drugs), as these are particularly toxic for people with A-T. The special problems of managing cancer are sufficiently complicated that treatment should be done only in academic oncology centers and after consultation with physicians who have specific expertise in A-T. Unfortunately, there is no way to predict which individuals will develop cancer. Because leukemia and lymphomas differ from solid tumors in not progressing from solitary to metastatic stages, there is less need to diagnose them early in their appearance. Surveillance for leukemia and lymphoma is thus not helpful, other than considering cancer as a diagnostic possibility whenever possible symptoms of cancer (e.g. persistent swollen lymph glands, unexplained fever) arise.

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