Ataxia Telangiectasia

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Contents 1 Etiology 2 Epidemiology 3 Pathology 4 Genetics 5 Clinical-manifestations 6 Laboratory 7 More General Terms 8 Additional Terms 9 Internet Database 10 References

Etiology

• mutation in ATM gene

Epidemiology

• most common of the degenerative ataxias

Pathology

• defect in DNA repair

• sensitivity to radiation
• increased recombinase-mediated interlocus rearrangements
• cells from patients with AT are defective at both the G1/S & G2/M checkpoints.
• DNA repair defect may account for the high incidence of malignancy in these patients

• loss of cerebellar Purkinje cells results in cerebellar ataxia
• immunodeficiency

• not all patients have immunodeficiency
• immunological abnormalities appear to be related to aberrant development of the thymus
• the thymus is markedly hypoplastic & similar in appearance to an embryonic thymus
• peripheral T-cells are frequently reduced in number, especially within lymphoid tissue
• cutaneous anergy is common.
• the number & distribution of B-cells is usually normal; however most patients are deficient in IgE & IgA, & some in IgG particularly IgG2 & IgG4
• IgM & IgD are usually normal

• 2 most common causes of death

• chronic pulmonary disease
• malignancy.

• lymphomas are the most common malignancy
• brain tumors occur as well

• insulin resistance with anti-insulin antibodies [1]

Genetics

• autosomal recessive
• the responsible gene, the ATM ( ataxia telangiectasia, mutated) gene has been mapped to chromosome 11q22-23
• other implicated genes: GADD45A

Clinical-manifestations

• cerebellar ataxia

• generally 1st neurologic sign in patients with AT
• progresses slowly, but relentlessly to severe disability
• truncal ataxia in infancy
• symptoms of ataxia manifesting at about 2 years of age, progressing to loss of ambulation by adolescence

• oculocutaneous telangiectasias

• telangiectasias are most obvious in the sclerae
• other areas are also affected
• telangiectasias may occur as early as 1 year of age or as late as 6 years

• other skin lesions

• hypo- & hyperpigmentation
• atopic dermatitis
• cutaneous atrophy simulating scleroderma
• nummular eczema

• oculomotor apraxia & horizontal nystagmus are common
• variable choreoathetoid or tic-like movements
• a mask-like facies with excessive drooling produces a remarkable similarity of appearance in affected patients
• muscle weakness
• poor reflexes
• intellectual development is normal at first, but seems to stop at about 10 years in many patients
• manifestations of immunodeficiency

• recurrent & chronic sino- pulmonary infection leading to bronchiectasis
• not all patients have immunodeficiency

Laboratory

• elevated embryonic proteins* in serum

• elevated alpha-fetoprotein ( AFP) &
• carcinoembryonic antigen ( CEA)

• * seen in virtually all patients with AT (consistent with abnormalities in embryogenesis)

More General Terms

• hereditary neoplastic syndrome; cancer susceptibility syndrome
• chromosomal instability syndrome
• cerebellar disease
• immunologic disease

Additional Terms

• ataxia telangiectasia-like disorder (ATLD)

Internet Database

OMIM: 208900

References

1. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1564, 1999, 2057
2. NINDS Ataxia Telangiectasia Information Page [1]

ataxia telangiectasia; Louis-Bar syndrome