Ataxia telangiectasia

Neurology

Clinicals - History

Fact Explanation
Introduction to the disease Ataxia telangiectasia (A-T) is autosomal recessively inherited progressive neurological disorder resulted due to cerebellar degeneration. It is usually found by the age of 2 years..There are classic form of A-T as well as non classic forms of Ataxia-Telangiectasia.. Diagnosis criteria of A-T include ataxia or significant motor incoordination with raised alpha fetoprotein (AFP) (>2x) and at least 3 of the following four characteristic clinical features.They are Incoordination of head and eyes in lateral gaze deflection,gait ataxia associated with an inappropriately narrow-base,ocular telangiectasia and Immunoglobulin deficiencies . Introduction to the disease
Ataxia telangiectasia (A-T) is autosomal recessively inherited progressive neurological disorder resulted due to cerebellar degeneration. It is usually found by the age of 2 years..There are classic form of A-T as well as non classic forms of Ataxia-Telangiectasia.. Diagnosis criteria of A-T include ataxia or significant motor incoordination with raised alpha fetoprotein (AFP) (>2x) and at least 3 of the following four characteristic clinical features.They are Incoordination of head and eyes in lateral gaze deflection,gait ataxia associated with an inappropriately narrow-base,ocular telangiectasia and Immunoglobulin deficiencies .
Progressive gait and truncal ataxia It is the primary manifestation of classic A-T and the age of onset between 1 to 4 years. It occurs due to cerebellar degeneration. Children with A-T begin to stagger, shortly after they learnt to walk. The ataxia initialy begins as purely truncal but later on, within several years peripheral coordination also get involved. Due to progressive nature children will confined to a wheelchair by the age of 10 years. Affected children have a peculiar gait like “little clowns” which is highly suggestive of A-T.. Progressive gait and truncal ataxia
It is the primary manifestation of classic A-T and the age of onset between 1 to 4 years. It occurs due to cerebellar degeneration. Children with A-T begin to stagger, shortly after they learnt to walk. The ataxia initialy begins as purely truncal but later on, within several years peripheral coordination also get involved. Due to progressive nature children will confined to a wheelchair by the age of 10 years. Affected children have a peculiar gait like “little clowns” which is highly suggestive of A-T..
Oculocutaneous telangiectasia Telangiectasia is a second major clinical manifestation of the disease and it has a later onset than ataxia..These are dilated vessels usually found at corners of eyes as well as on the surface of the ears and cheeks which usually exposed to sunlight. The underline mechanism of telangiectasia is not clear. However they are found after the age of 3-6 years and sometimes not notice until adolescence .. Telangiectasia can seen in different parts of the body, but most noticeable in bulbar conjunctiva. . Oculocutaneous telangiectasia
Telangiectasia is a second major clinical manifestation of the disease and it has a later onset than ataxia..These are dilated vessels usually found at corners of eyes as well as on the surface of the ears and cheeks which usually exposed to sunlight. The underline mechanism of telangiectasia is not clear. However they are found after the age of 3-6 years and sometimes not notice until adolescence .. Telangiectasia can seen in different parts of the body, but most noticeable in bulbar conjunctiva. .
Slurred speech Slurred speech is also found in early stage of the disease.. Occurs due to involvement of cerebellum.. Slurred speech
Slurred speech is also found in early stage of the disease.. Occurs due to involvement of cerebellum..
Poor head control Poor control of head and torso is identified By the end of first decade.. Head tilt occurs due to defect in the vermal zone of the cerebellum. Poor head control
Poor control of head and torso is identified By the end of first decade.. Head tilt occurs due to defect in the vermal zone of the cerebellum.
Difficulty in swallowing Swallowing is not well coordinated in affected individuals. They need others help for eating. Aspiration of food can be occur.. Difficulty in swallowing
Swallowing is not well coordinated in affected individuals. They need others help for eating. Aspiration of food can be occur..
Learning difficulties Intelligence is found to be normal but learning difficulties are common. Individuals may face difficulty in completing timed IQ tests due to low motor and verbal responses.. Learning difficulties
Intelligence is found to be normal but learning difficulties are common. Individuals may face difficulty in completing timed IQ tests due to low motor and verbal responses..
Frequent infections The spectrum of infection in classic A-T doesn't include opportunistic infections. The frequency as well as severity of infections are found to be correlates with patients general nutritional status than with the immune status. Chronic bronchiectasis seen in patients with classic A-T.. There is an increase risk for lower respiratory tract infections with age mostly due to aspiration of food as a result of impaired swallowing as well as deficient cough reflex.. Frequent infections
The spectrum of infection in classic A-T doesn't include opportunistic infections. The frequency as well as severity of infections are found to be correlates with patients general nutritional status than with the immune status. Chronic bronchiectasis seen in patients with classic A-T.. There is an increase risk for lower respiratory tract infections with age mostly due to aspiration of food as a result of impaired swallowing as well as deficient cough reflex..
Growth retardation It is frequently detected in affected individuals. . Premature aging can also detect in some patients.. Growth retardation
It is frequently detected in affected individuals. . Premature aging can also detect in some patients..
Immunodeficiency Serum and cellular immunodeficiencies can be seen. It seen among 60% to 80% of individuals. Serum concentration of immunoglobulins including IgA, IgE, and IgG2 may be reduced. T-cell deficiencies found in 30% of affected patients with classic AT. Immunodeficiency is non progressive.. Immunodeficiency
Serum and cellular immunodeficiencies can be seen. It seen among 60% to 80% of individuals. Serum concentration of immunoglobulins including IgA, IgE, and IgG2 may be reduced. T-cell deficiencies found in 30% of affected patients with classic AT. Immunodeficiency is non progressive..
Thymic dysplasia Absence or dysplasia of thymus gland is found in some patients.. Thymic dysplasia
Absence or dysplasia of thymus gland is found in some patients..
Risk of malignancy The risk of developing cancer in a classic AT patient is approximately 38%. Leukemia and lymphoma are found to be responsible for about 85% of malignancies. Acute lymphocytic leukemia (ALL) of T-cell origin seen among young children and aggressive T-cell leukemia can occur in older children. Lymphomas are usually B-cell types. Ovarian c, breast , and gastric cancers, as well as melanoma, leiomyomas, and sarcomas are also reported in affected individuals.. Risk of malignancy
The risk of developing cancer in a classic AT patient is approximately 38%. Leukemia and lymphoma are found to be responsible for about 85% of malignancies. Acute lymphocytic leukemia (ALL) of T-cell origin seen among young children and aggressive T-cell leukemia can occur in older children. Lymphomas are usually B-cell types. Ovarian c, breast , and gastric cancers, as well as melanoma, leiomyomas, and sarcomas are also reported in affected individuals..
Drooling Drooling of saliva is commonly found in A-T patients.. Drooling
Drooling of saliva is commonly found in A-T patients..
Endocrine abnormality Endocrine abnormalities seen in some patients, such as insulin resistant diabetes mellitus.. Endocrine abnormality
Endocrine abnormalities seen in some patients, such as insulin resistant diabetes mellitus..
Early death They have decreased life span.But somehow recently their life expectancy have been increased. Most affected individuals may live beyond 25 years and some have survived up to 50 years. Pulmonary failure, and infections are found to be major causative factors for death where some may develop life threatening lymphocytic infiltration of the lung.. Early death
They have decreased life span.But somehow recently their life expectancy have been increased. Most affected individuals may live beyond 25 years and some have survived up to 50 years. Pulmonary failure, and infections are found to be major causative factors for death where some may develop life threatening lymphocytic infiltration of the lung..

Clinicals - Examination

Fact Explanation
Oculomotor apraxia It means inability to follow an object across visual fields. Also identified in early stage of the disease. Here the both horizontal and vertical saccadic eye movements are get affected.. Oculomotor apraxia
It means inability to follow an object across visual fields. Also identified in early stage of the disease. Here the both horizontal and vertical saccadic eye movements are get affected..
Absent or decreased tendon reflexes Deep tendon reflexes are found to be decreased or absent in older individuals. Up going or absent plantar reflexes can be identified. . Absent or decreased tendon reflexes
Deep tendon reflexes are found to be decreased or absent in older individuals. Up going or absent plantar reflexes can be identified. .
Myoclonic jerking and intention tremors About 25% of individuals may reported to have myoclonic jerking and intention tremors.. kinetic tremor occurs due to defect in the lateral zone of the cerebellum.. Myoclonic jerking and intention tremors
About 25% of individuals may reported to have myoclonic jerking and intention tremors.. kinetic tremor occurs due to defect in the lateral zone of the cerebellum..
Contractures Even though the muscle strength is normal at first, it wanes with disuse, specially in the legs. This will cause formation of contractures commonly in the fingers and toes in older individuals.. Contractures
Even though the muscle strength is normal at first, it wanes with disuse, specially in the legs. This will cause formation of contractures commonly in the fingers and toes in older individuals..
Dystonia Dystonia also found in affected individuals.. It is a manifestation of extra pyramidal deficits.. Dystonia
Dystonia also found in affected individuals.. It is a manifestation of extra pyramidal deficits..
Choreoathetosis They are writhing movements that found in almost all patients with A-T..Choreiform movements commonly seen in hands and feet.. Choreoathetosis
They are writhing movements that found in almost all patients with A-T..Choreiform movements commonly seen in hands and feet..

Investigations - Diagnosis

Fact Explanation
Serum concentration of alpha-fetoprotein (AFP). Diagnosis is established with the help of characteristic clinical symptoms as well as laboratory investigation findings.Serum AFP concentration is found to be elevated above 10 ng/mL in more than 95% of individuals with A-T. However serum AFP levels may remain above normal in unaffected children up to the age of 2 years.. Serum concentration of alpha-fetoprotein (AFP).
Diagnosis is established with the help of characteristic clinical symptoms as well as laboratory investigation findings.Serum AFP concentration is found to be elevated above 10 ng/mL in more than 95% of individuals with A-T. However serum AFP levels may remain above normal in unaffected children up to the age of 2 years..
Immunoblotting for ATM protein This test is the most sensitive and specific clinical test to establish the diagnosis of A-T. Intracellular ATM protein level is found to be severely depleted in affected individuals. But this needs further validation.. Immunoblotting for ATM protein
This test is the most sensitive and specific clinical test to establish the diagnosis of A-T. Intracellular ATM protein level is found to be severely depleted in affected individuals. But this needs further validation..
Radiosensitivity assay The colony survival assay (CSA) is an in vitro assay. It is carried out to determine the survival of patient derived lymphoblastoid cells following irradiation with 1.0 Gy. Increased sensitivity of cells to radiation exposure can be seen in affected individuals.. Radiosensitivity assay
The colony survival assay (CSA) is an in vitro assay. It is carried out to determine the survival of patient derived lymphoblastoid cells following irradiation with 1.0 Gy. Increased sensitivity of cells to radiation exposure can be seen in affected individuals..
ATM serine/threonine kinase activity. Immunoblotting of cell lysates and commercial antibodies to many phosphorylated ATM target substrates such as p53-serine15 are the procedures that performed to assess ATM serine/threonine kinase activity. Cells are first irradiated and evaluated after 30 minutes. ATM serine/threonine kinase activity is found to be undetectable in all cases where ATM protein levels are undetectable.. ATM serine/threonine kinase activity.
Immunoblotting of cell lysates and commercial antibodies to many phosphorylated ATM target substrates such as p53-serine15 are the procedures that performed to assess ATM serine/threonine kinase activity. Cells are first irradiated and evaluated after 30 minutes. ATM serine/threonine kinase activity is found to be undetectable in all cases where ATM protein levels are undetectable..
Serum immunoglobulin assay Impaired immunological status is a feature of almost all AT patients.Serum IgA and IgE levels may be decreased or absent. 50-80% of affected individuals show selective IgA deficiency.IgG4 subclass levels reduced in some individuals.. Serum immunoglobulin assay
Impaired immunological status is a feature of almost all AT patients.Serum IgA and IgE levels may be decreased or absent. 50-80% of affected individuals show selective IgA deficiency.IgG4 subclass levels reduced in some individuals..
MRI brain It will show a small cerebellum,/ cerebellar atrophy.However it is not usually apparent in young children.,. MRI brain
It will show a small cerebellum,/ cerebellar atrophy.However it is not usually apparent in young children.,.
Chromosome analysis. 5%-15% of peripheral blood cells in A-T patients show chromosome translocation. The break points are commonly at 14q11 and 14q32.. Chromosome analysis.
5%-15% of peripheral blood cells in A-T patients show chromosome translocation. The break points are commonly at 14q11 and 14q32..
Molecular Genetic Testing ATM gene is the only gene known to be associated with ataxia-telangiectasia. Molecular genetic testing reveals mutations in ATM gene, greater than 99% of individuals with classic A-T.. Molecular Genetic Testing
ATM gene is the only gene known to be associated with ataxia-telangiectasia. Molecular genetic testing reveals mutations in ATM gene, greater than 99% of individuals with classic A-T..

Investigations - Management

Fact Explanation
CEA and AFP levels A-T patients tend to develop variety of cancers. They tend to have elevated AFP and CEA, which are tumor markers. Changes in these tumor markers levels can be used to early cancer detection during follow-up.. CEA and AFP levels
A-T patients tend to develop variety of cancers. They tend to have elevated AFP and CEA, which are tumor markers. Changes in these tumor markers levels can be used to early cancer detection during follow-up..
Serum immunoglobulin levels Has to assess during follow up because affected individuals prone to get immunodeficiency as well as recurrent infections.. Serum immunoglobulin levels
Has to assess during follow up because affected individuals prone to get immunodeficiency as well as recurrent infections..
Full blood count FBC with differential count is performed as a baseline investigation for screening for leukemia.. Full blood count
FBC with differential count is performed as a baseline investigation for screening for leukemia..
Chest x-ray and pulmonary function Since A-T patients prone to develop recurrent lower respiratory tract infections baseline Chest x-ray and pulmonary function test should be performed.. Chest x-ray and pulmonary function
Since A-T patients prone to develop recurrent lower respiratory tract infections baseline Chest x-ray and pulmonary function test should be performed..
Fasting blood glucose concentration and Hgb A1C Urinalysis, fasting blood glucose concentration and Hgb A1C levels used as diabetes screening tests since A-T patients may develop endocrine abnormalities such as insulin resistant diabetes mellitus.. Fasting blood glucose concentration and Hgb A1C
Urinalysis, fasting blood glucose concentration and Hgb A1C levels used as diabetes screening tests since A-T patients may develop endocrine abnormalities such as insulin resistant diabetes mellitus..
Amniocentesis or chorionic villus sampling Performed in prenatal diagnosis in pregnancies.Analysis of DNA extracted from fetal cells is carried out Those DNA is extracted either by amniocentesis performed around ~15-18 weeks’ gestation or chorionic villus sampling performed around ~10-12 weeks’ gestation.. Amniocentesis or chorionic villus sampling
Performed in prenatal diagnosis in pregnancies.Analysis of DNA extracted from fetal cells is carried out Those DNA is extracted either by amniocentesis performed around ~15-18 weeks’ gestation or chorionic villus sampling performed around ~10-12 weeks’ gestation..

Management - Supportive

Fact Explanation
Physiotheraphy Carried out to minimize contractures. Early and continued physical therapy is useful in minimizing development of contractures thereby improving quality of life. And also prolonged time in a wheelchair may leads to serious complications such as scoliosis. It can prevent by aggressive physical therapy.. Physiotheraphy
Carried out to minimize contractures. Early and continued physical therapy is useful in minimizing development of contractures thereby improving quality of life. And also prolonged time in a wheelchair may leads to serious complications such as scoliosis. It can prevent by aggressive physical therapy..
Aggressive pulmonary hygiene Useful in patients with chronic bronchiectasis .. Pulmonary infections well respond to antibiotics.. Aggressive pulmonary hygiene
Useful in patients with chronic bronchiectasis .. Pulmonary infections well respond to antibiotics..
Treatment for dysfunctional swallowing and aspiration Thickeners to thin liquids and in case of severe malnutrition,the placement of a gastroscopy tube can use to facilitate feeding.. Treatment for dysfunctional swallowing and aspiration
Thickeners to thin liquids and in case of severe malnutrition,the placement of a gastroscopy tube can use to facilitate feeding..
Reduce the intensity of radiotherapy and dosage of radiomimetic chemotherapy A-T patients are hypersensitive to ionizing radiation. These measures are carried out to minimize tissue damage in patients while retaining effectiveness of treatment of the tumor. Some chemotherapeutic agents are better to be avoid. Cyclophosphamide may cause haemorrhagic cystitis and gastrointestinal toxicity may caused by methotrexate.. Reduce the intensity of radiotherapy and dosage of radiomimetic chemotherapy
A-T patients are hypersensitive to ionizing radiation. These measures are carried out to minimize tissue damage in patients while retaining effectiveness of treatment of the tumor. Some chemotherapeutic agents are better to be avoid. Cyclophosphamide may cause haemorrhagic cystitis and gastrointestinal toxicity may caused by methotrexate..
Genetic councelling It is "the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions." Since this is a autosomal recessively inherited disease genetic counselling is a must. Family members and patient should educate about the carrier detection methods as well as the family planing methods.. Genetic councelling
It is "the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions." Since this is a autosomal recessively inherited disease genetic counselling is a must. Family members and patient should educate about the carrier detection methods as well as the family planing methods..
Proper counselling, patient and family education. Once diagnosis is established proper counselling should be carried out by the doctor with the explanation of nature of the disease, life expectancy and complications. Educate them well regarding the malignancy and infection risk and there by importance of proper follow up. Tell the family members that patient can not do their day today works alone and they may need family members helping hand. Tell them that patient may need a wheelchair probably at the age of 10 years.. Proper counselling, patient and family education.
Once diagnosis is established proper counselling should be carried out by the doctor with the explanation of nature of the disease, life expectancy and complications. Educate them well regarding the malignancy and infection risk and there by importance of proper follow up. Tell the family members that patient can not do their day today works alone and they may need family members helping hand. Tell them that patient may need a wheelchair probably at the age of 10 years..

Management - Specific

Fact Explanation
IV immunoglobulin replacement therapy It should be carried out in patients with frequent and severe infections and also who have a very low IgG levels.. IV immunoglobulin replacement therapy
It should be carried out in patients with frequent and severe infections and also who have a very low IgG levels..
L-DOPA derivatives, dopamine agonists and, anticholinergics Slight improvement of neurological symptoms and basal ganglia dysfunction in respond to these treatments can be seen. Anticholinergics may useful in reducing drooling.. L-DOPA derivatives, dopamine agonists and, anticholinergics
Slight improvement of neurological symptoms and basal ganglia dysfunction in respond to these treatments can be seen. Anticholinergics may useful in reducing drooling..
Amantadine and fluoxetine The loss of balance may respond to amantadine, buspiron or fluoxetine like antidepressant agents. These drugs may also found to improve speech and coordination.. Amantadine and fluoxetine
The loss of balance may respond to amantadine, buspiron or fluoxetine like antidepressant agents. These drugs may also found to improve speech and coordination..
Beta blockers Propanalol like beta blockers useful to control tremors.. Beta blockers
Propanalol like beta blockers useful to control tremors..
Steroids Recent studies have showed short-term improvement in ataxia can be seen after treat with steroids but tends to reappear within days of their discontinuation. However its side effect profile overcomes this short term benefit.,. Steroids
Recent studies have showed short-term improvement in ataxia can be seen after treat with steroids but tends to reappear within days of their discontinuation. However its side effect profile overcomes this short term benefit.,.

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