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Ataxia-Telangiectasia: Differential Diagnoses & Workup

Author: Sergiusz Jozwiak, MD, PhD, Head, Professor, Department of Child Neurology, The Children's Memorial Health Institute of Warsaw, Poland
Coauthor(s): Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School; Tomasz Kmiec, MD, Adjunct Senior Assistant, Department of Child Neurology, Children's Memorial Health Institute of Warsaw, Poland; Ewa Bernatowska, MD, Head, Department of Immunology, The Children's Memorial Health Institute of Warsaw, Poland
Contributor Information and Disclosures

Updated: Jan 7, 2009

Differential Diagnoses

[Gaucher Disease]
Acanthosis Nigricans
Hartnup Disease
Niemann-Pick Disease
Nijmegen Breakage Syndrome
Refsum Disease

Other Problems to Be Considered

Friedreich disease
Cerebral palsy (cerebellar type)
Familial spinocerebellar atrophies
GM1 and GM2 gangliosidoses
Metachromatic leukodystrophy
Krabbe disease
Maple syrup urine disease
Progressive rubella panencephalitis
Subacute sclerosing panencephalitis
Postinfectious encephalomyelitis
Encephalitis
Other polyneuropathies
Cerebellar tumor

Workup

Laboratory Studies

  • Laboratory markers are important for both diagnosis and prognosis. The most constant markers are elevated levels of AFP and carcinoembryonic antigen and chromosomal abnormalities, especially inversions and translocations involving chromosomes 7 and 14, though neither of these abnormalities is always found and their demonstration requires specific techniques available in only a few centers.
    • The demonstration of humoral or cellular immunologic defects may also permit an early diagnosis, although such defects are nonspecific and present less frequently.
    • The dysgammaglobulinemia of ataxia-telangiectasia includes an absent or low level of IgA, including secretory IgA, a normal or low level of IgG, and an elevated or normal level of IgM. IgA deficiency is found in about 70% of patients with ataxia-telangiectasia syndrome.
    • A deficit in IgG2 and IgG4 subclasses has been demonstrated in several patients, and IgE may also be absent or low.
    • Defects of cellular immunity include a low lymphocyte count, a poor response to skin tests to common antigens, low T-lymphocyte proliferation in the presence of mitogens, and deficient antibody production to viral or bacterial antigens.
    • Excessive T-cell suppressor activity and intrinsic B-cell defects have been described in some patients, suggesting disturbances of immunoregulatory mechanisms.
    • The incidence of immunologic abnormalities increases with the age of the patients.
  • Increased chromosomal breakage after exposure of cell cultures to ionizing radiation is rapidly increasing diagnostic importance, though not yet a routine procedure. Such tests have been considered for the prenatal diagnosis of ataxia-telangiectasia but are being supplanted by DNA diagnosis.
  • Protein-truncation testing of the entire ATM complementary DNA (cDNA) reveals as much as 66% of truncating mutations in the group with mutant alleles. These rapid assays detected mutations in 76% of Costa Rican patients, 50% of Norwegian patients, 25% of Polish patients, and 14% of Italian patients.

Imaging Studies

  • MRI and sporadically made CT scan often show evidence of nonspecific cerebellar atrophy with widened cerebellar sulci and enlargement of the fourth ventricle. According to Tavani et al, cerebellar atrophy found on MRIs progresses with age, starting from early childhood.30 Cerebral white matter dysmyelination or demyelination, microhemorrhages and teleangiectases also are reported.28   
  • Radiologic findings of decreased or absent adenoidal tissue in the nasopharynx on lateral skull radiographs are so typical in ataxia-telangiectasia that they are of value in confirming the diagnosis.
    • Chest radiographs may show a small or absent thymic shadow, decreased mediastinal lymphoid tissue, and pulmonary changes similar to those seen in cystic fibrosis.
    • Hypoplastic peripheral lymphoid tissue is such a consistent clinical finding in ataxia-telangiectasia that the appearance of lymphadenopathy or even easily palpable lymph nodes has been highly suggestive of lymphoma.

Other Tests

  • Electromyogram (EMG) and nerve conduction velocities are frequently normal in small children. In later stages of the disease, when the anterior horn cells are involved and peripheral neuropathy has occurred, the EMG shows signs of denervation and the nerve conduction velocity is reduced, especially in sensory fibers.
  • Electrooculography is valuable in corroborating the characteristic oculomotor abnormality of ataxia-telangiectasia and differentiating ataxia-telangiectasia from Friedreich ataxia.

Histologic Findings

The major pathological marker of ataxia-telangiectasia in the CNS is degeneration of Purkinje and granule cells in the cerebellum. No vascular abnormalities are usually found, except late degenerative gliovascular nodules in the white matter. Lesions of the basal ganglia are found only occasionally. Degeneration of spinal tracts and anterior horn cells is often present in late cases. Nucleocytomegaly is a feature of several cell types throughout the body.

Biopsy specimens have shown that the typical skin changes in ataxia-telangiectasia are similar to those seen in cumulative actinic damage and, thus, are suggestive of progeric changes. The predilection of both the progeric skin changes and the oculocutaneous telangiectases for sun-exposed areas further suggests increased propensity to actinic damage.

More on Ataxia-Telangiectasia

Overview: Ataxia-Telangiectasia
Differential Diagnoses & Workup: Ataxia-Telangiectasia
Treatment & Medication: Ataxia-Telangiectasia
Follow-up: Ataxia-Telangiectasia
Multimedia: Ataxia-Telangiectasia
References
[ CLOSE WINDOW ]

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Further Reading

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Keywords

ataxia-telangiectasia, A-T, AT, Louis-Bar syndrome, Boder-Sedgwick syndrome

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Contributor Information and Disclosures

Author

Sergiusz Jozwiak, MD, PhD, Head, Professor, Department of Child Neurology, The Children's Memorial Health Institute of Warsaw, Poland
Sergiusz Jozwiak, MD, PhD is a member of the following medical societies: Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Camila K Janniger, MD, Clinical Professor of Dermatology, Clinical Associate Professor of Pediatrics, Chief of Pediatric Dermatology, New Jersey Medical School
Camila K Janniger, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Tomasz Kmiec, MD, Adjunct Senior Assistant, Department of Child Neurology, Children's Memorial Health Institute of Warsaw, Poland
Disclosure: Nothing to disclose.

Ewa Bernatowska, MD, Head, Department of Immunology, The Children's Memorial Health Institute of Warsaw, Poland
Disclosure: Nothing to disclose.

Medical Editor

Albert C Yan, MD, Section Chief, Associate Professor, Department of Pediatrics, Section of Dermatology, Children's Hospital of Philadelphia and University of Pennsylvania
Albert C Yan, MD is a member of the following medical societies: American Academy of Dermatology, American Academy of Pediatrics, Society for Investigative Dermatology, and Society for Pediatric Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: 3M Pharmaceutical Grant/research funds Other; Graceway Pharmaceuticals Grant/research funds Other

Managing Editor

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

CME Editor

Glen H Crawford, MD, Assistant Clinical Professor, Department of Dermatology, University of Pennsylvania School of Medicine; Chief, Division of Dermatology, The Pennsylvania Hospital
Glen H Crawford, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, Phi Beta Kappa, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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