A Bangladeshi Child with Ataxia Telangiectasia

Ataxia Telangiectasia:

Ataxia telangiectasia is a rare, neurodegenerative, inherited disease that affects many parts of the body and causes severe disability.

Ataxia refers to poor coordination of movement, including wide-based, uncoordinated, unsteady gait due to dysfunction of the cerebellum and telangiectasia refers to small dilated blood vessels and capillaries usually of the sclera, face and ears. Both of which are hallmarks of the disease.

Case Summary

Khadiza, 9 years old girl, the 1st  issue of consanguineous parents hailing from Cumilla presented with complaints of difficulty in walking in the form of ataxia for 7 years which had been progressive. She also had difficulty holding a pen and writing smoothly, was unable to participate in sports and has had dysarthria for the last 2 years. H/O repeated upper RTI at 1-2 months intervals for the last 4 years and treated with antibiotics with recovery each time.

She had no history of headache, lethargy, vomiting, convulsion, unconsciousness, head trauma, chronic exposure to toxins, palpitations, abnormal sensation or skeletal deformity, bruising, localized pain or swelling, weight loss and family history of such type of illness.

On examination, she was conscious, alert, cooperative, and mildly pale, Eye – Telangiectasia was present in the conjunctiva of both eyes.  Vitals were within normal limits. Anthropometrically thriving well. The nervous system examination revealed higher psychic functions normal except for dysarthria. The cranial nerve examination revealed normal findings. Motor system examination revealed bulk symmetrically normal, hypotonia, and power 4/5 in all limbs. DTR – normal, planter – Flexor, coordination impaired with an ataxic gait.

All modalities of sensations were intact. Romberg signs – Negative. Cerebellar sign – Positive. Other systemic examinations revealed no abnormality.

From history and clinical examination, the provisional diagnosis is Ataxia Telangiectasia.

Friedreich’s  Ataxia is a differential diagnosis.

Why it is a case of ataxia telangiectasia?

Points in Favour

1. Consanguinity
2. Age is suggestive
3. Walking, writing and speech difficulty
4. Cerebellar dysfunction
5. Ocular Telangiectasia
6. Repeated RTI
7. Cognition – Normal
8. No sensory abnormality

For Friedreich’s  Ataxia

Points in Favour

1. Consanguinity
2. Ataxia
3. Cerebellar signs

Points against

1. Sense of position, vibration intact
2. No pyramidal tract sign
3. Rombergꞌs Negative
4. No scoliosis, pes cavus
5. No cardiac involvement

How to investigate to confirm ataxia telangiectasia?

Plan of investigations:

• MRI of Brain
• Immunoglobulin Panel
• Serum alpha-fetoprotein
• CBC
• RBS
• Eye evaluation
• Genetic study

MRI of the Brain:

Biochemical Investigations:

• IgG level : 12.10 g/l ( 7-16g/l)
• Ig M level: 1.28 g/l ( 0.4-2.3g/l)
• Ig A level : 0.66 g/l (0.70- 4g/l)
• Ig E level : 160 IU/ml (< 200 IU/ml)
• α fetoprotein : 153 ng/ml (15ng/ml)
• Fasting Blood Sugar: 6.5 mmol/l

CBC with PBF: Nonspecific

Eye Examination:

1. Ocular telangiectasia on bulbar conjunctiva sparing limbus
2. Visual acuity: Right- 6/6   Left-6/6
3. Anterior and Posterior chamber – WNL
4. Fundoscopy – Normal

Treatment on Admission:

1. Counselling about the disease, treatment and prognosis
2. Vitamin E
3. Folic Acid
4. Enzyme Co Q 10
5. Fexofenadine as antihistamine
6. Physiotherapy and Occupational Therapy
7. Immunization

What is Ataxia:

The word “Ataxia” is derived from the Greek word ataktos, which means “lack of order.” Ataxia may be defined as  -Impaired coordination of voluntary muscle movement which is caused by cerebellar dysfunction or impaired vestibular or proprioceptive afferent input to the cerebellum.

There are 3 types of ataxia

1. Cerebellar
2. Vestibular
3. Proprioceptive/Sensory

Types of cerebellar ataxia

Genetics of the disease:

1. Ataxia telangiectasia is caused by sequence disruption in the ATM gene .
2. It is an autosomal recessive disorder.
3. Family of 2 parents who are carriers of A- T, there is 1 chance in 4 that each child born to the parents will have the disorder.
4. If the parents carry one copy of the gene, they themselves won’t be affected by it, but they will be carriers.

Symptoms and Signs of ataxia-telangiectasia:

1. At first, infants with A-T appear healthy. By age 2, however, parents notice increased clumsiness and balance problems. As symptoms become progressively worse, speech becomes slurred and difficult.
2. Between ages 2 to 8, the telangiectasias – tiny, red “spider” veins – appear on the cheeks, ears, and in eyes.
3. By age 10 to 12, children with A-T lose muscle control.
4. Immune system deficiencies, low immunoglobulin concentrations.
5. The missing or abnormally developed thymus gland,
6. Endocrine abnormalities: retarded growth, diabetes, hypogonadism
7. prematurely ageing of hair and skin, and difficulty swallowing
8. Oculomotor apraxia (difficulty following objects across visual  field
9. Telangiectasias of the eyes and skin (nasal bridge, auricle, antecubital fossa, popliteal space, upper chest
10. Chromosomal instability
11. Hypersensitivity to ionizing radiation
12. Increased incidence of malignancies (primarily hematologic)
13. Dystonia, choreoathetosis, myoclonus.
14. Progressive spine muscular atrophy and peripheral neuropathy.
15. cafe-au-lait spot, vitiligo, scleroderma-like lesions.
16. Ovarian dysgenesis.

Investigation findings in Ataxia telangiectasia

1. Alfa fetoprotein – elevated ( >10 ng/ml in 90% cases of classic AT)
2. CEA (carcinoembryonic antigen)- elevated
3. Immunoglobulins-
4. Serum Ig A and Ig E-  Decreased or absent
5. Serum Ig M, G1 and G3 – Normal or increased
6. Immunoglobulin G2 and G4 – Decreased
7. MRI of brain –nonspecific cerebellar atrophy with widened cerebellar sulci and enlargement of 4th ventricle .
8. RBS
9. Genetic analysis (for ATM gene)

Antenatal diagnosis can be done through direct gene analysis.

How to treat?

Symptomatic Treatment:

1. There is only symptomatic and supportive treatment.
2. Physical, occupational and speech therapy and exercise may help maintain function.
3. Antioxidants- vitamin E, Coenzyme Q 10, Folic acid.
4. For Basal ganglia dysfunction – anticholinergics,  L-DOPA derivatives.
5. For tremor – propranolol, clonazepam, gabapantine
6. For severe recurrent infection and low immunoglobulin levels- IVIG
7. Antibiotics to treat the infection.
8. Chronic bronchiectasis- aggressive pulmonary hygiene.
9. For balance and impaired speech-  Amantidine, fluoxetine or buspirone.
10. Low-dose chemotherapy reduces the risk of cancer (controversial).
11. Glucocorticoids.
12. Desferrioxamine – increases the stability of AT cells.
13. Additional vaccination.
14. Avoid exposure to ionizing radiation.

Specific treatment:

1. There is no specific treatment.
2. On trial –Gene therapy, Stem cell therapy

Prognosis:

1. The average life span nowadays is improving. Most die in their teens or early 20s. Some have survived into their 40s-50s.
2. People with A-T have an increased incidence (probably 1% per year) of tumours, particularly leukaemia and lymphoma.
3. Sensitivity to radiotherapy, chemotherapy and ionizing radiation.
4. ATM carriers die 7-8 years earlier than the normal population.
5. Single ATM mutation also had a high risk of cancers.

Thank you.

Ataxia Telangiectasia Children’s Society www.atcp.org

Download AT Guideline Management PDF

Multidisciplinary Management of Ataxia Telangiectasia: Current Perspectives www.ncbi.nlm.nih.gov