Clinical manifestations in Iranian Ataxia Telangiectasia Patients

Document Type : Original Article


Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Science, Tehran, Iran




Introduction: Ataxia telangiectasia (AT) is an autosomal recessive primary immunodeficiency (PID) disease with multisystem involvement caused by biallelic mutations in the ataxia telangiectasia mutated (ATM) gene. The patients with AT represent a broad range of clinical manifestations including progressive cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, and susceptibility to malignancies. We aimed to determine different clinical features of the AT patients to identify their key diagnostic or prognostic characteristics.
Methods: In the present study, 120 patients with the confirmed diagnosis of AT were enrolled from Iranian immunodeficiency registry center. A demographic information, clinical complications, and laboratory data were obtained from all the patients to evaluate the clinical manifestations.
Results: In this study, we found that in the AT patients, the frequency of total infection, respiratory infection, gastrointestinal infection, urinary tract infection, chronic fever, lymphadenopathy, and hepatosplenomegaly were 83.3%, 68.3%, 18%, 6.7%, 26.7%, 7.5%, and 20%, respectively.
Conclusion: The AT patients present different types of infections and noninfectious complications; therefore, early detection and careful management is necessary for these patients.


1. Nissenkorn A, Levy-Shraga Y, Banet-Levi Y, Lahad A, Sarouk I, Modan-Moses D. Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort. Pediatr Res. 2016;79(6):889. 2. Van Os NJ, Haaxma CA, van der Flier M, Merkus PJ, van Deuren M, de Groot IJ, et al. Ataxia-telangiectasia: recommendations for multidisciplinary treatment. Dev Med Child Neurol. 2017;59(7): 680-9. 3. Amirifar P, Ranjouri MR, Yazdani R, Abolhassani H, Aghamohammadi A. Ataxia- telangiectasia: A review of clinical features and molecular pathology. Pediatr Allergy Immunol. 2019;30(3): 277-88. 4. Chaudhary MW, Al-Baradie RS. Ataxia- telangiectasia: future prospects. The application of clinical genetics. 2014;7: 159. 5. Gilad S, Chessa L, Khosravi R, Russell P, Galanty Y, Piane M, et al. Genotype-phenotype relationships in ataxia-telangiectasia and variants. Am J Hum Genet. 1998;62(3): 551-61. 6. Gatti RA, Berkel I, Boder E, Braedt G, Charmley P, Concannon P, et al. Localization of an ataxia-telangiectasia gene to chromosome 11q22–23. Nature. 1988;336(6199):577. 7. Lavin MF. Ataxia-telangiectasia: from a rare disorder to a paradigm for cell signalling and cancer. Nat Rev Mol Cell Bio. 2008;9(10):759-69. 8. Amirifar P, Yazdani R, Moeini Shad T, Ghanadan A, Abolhassani H, Lavin M, et al. Cutaneous Granulomatosis and Class Switching Defect as a Presenting Sign in Ataxia- Telangiectasia: First Case from the National Iranian Registry and Review of the Literature. Immunol Invest. 2019; 1-14. 9. McGrath-Morrow SA, Gower WA, RothblumOviatt C, Brody AS, Langston C, Fan LL, et al. Evaluation and management of pulmonary disease in ataxia-telangiectasia. Pediatr Pulmonol. 2010;45(9): 847-59. 10. Swift M, Morrell D, Cromartie E, Chamberlin A, Skolnick M, Bishop D. The incidence and gene frequency of ataxia-telangiectasia in the United States. Am J Hum Genet. 1986;39(5): 573 p. 11. Verhagen M, Abdo W, Willemsen M, Hogervorst F, Smeets D, Hiel J, et al. Clinical spectrum of ataxia-telangiectasia in adulthood. Neurology. 2009;73(6):430-7. 12. Chun HH, Gatti RA. Ataxia–telangiectasia, an evolving phenotype. DNA repair. 2004;3(8-13. Su Y, Swift M. Mortality rates among carriers of ataxia-telangiectasia mutant alleles. Ann Intern Med. 2000;133(10):770-8. 14. Crawford TO, Skolasky R, Fernandez R, Rosquist K, Lederman HM. Survival probability in ataxia telangiectasia. Arch Dis Child. 2006;91(7):610-1. 15. Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM. Immunodeficiency and infections in ataxia- telangiectasia. J pediatr. 2004;144(4):505-11. 16. Paganelli R, Scala E, Scarselli E, Ortolani C, Cossarizza A, Carmini D, et al. Selective deficiency of CD4+/CD45RA+ lymphocytes in patients with ataxia-telangiectasia. J Clin Immunol. 1992;12(2):84-91. 17. Schubert R, ZIELEN S. Deficiencies in CD4+ and CD8+ T cell subsets in ataxia telangiectasia. Clin Exp Immunol. 2002;129(1):125-32. 18. Goodman JS, van Uden JH, Kobayashi H, Broide D, Raz E, Feng D, et al. Serum IgD concentrations in patients with ataxia telangiectasia and with selective IgA deficiency. Int Arch Allergy Immunol. 1998;116(3):246. 19. Oxelius V-A, Berkel AI, Hanson LÅ. IgG2 deficiency in ataxia-telangiectasia. N Engl J Med. 1982;306(9):515-7. 20. Sanal O, Ersoy F, Yel L, Tezcan I, Metin A, Özyürek H, et al. Impaired IgG antibody production to pneumococcal polysaccharides in patients with ataxia–telangiectasia. J clin immunol. 1999;19(5):326-34. 21. Chopra C, Davies G, Taylor M, Anderson M, Bainbridge S, Tighe P, et al. Immune deficiency in Ataxia-Telangiectasia: a longitudinal study of 44 patients. Clin Exp Immunol. 2014;176(2):275-82. 22. Abolhassani H, Kiaee F, Tavakol M, Chavoshzadeh Z, Mahdaviani SA, Momen T, et al. Fourth Update on the Iranian National Registry of Primary Immunodeficiencies: Integration of Molecular Diagnosis. J clin immunol. 2018;38(7):816-32. 23. Seidel MG, Kindle G, Gathmann B, Quinti I, Buckland M, van Montfrans J, et al. The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity. J Allergy Clin Immunol Pract. 2019;7(6):1763-1770 24. Moin M, Aghamohammadi A, Kouhi A, Tavassoli S, Rezaei N, Ghaffari SR, et al. Ataxia- telangiectasia in Iran: clinical and laboratory features of 104 patients. Pediatr Neurol. 2007;37(1):21-8. 25. Rezaei N, Pourpak Z, Aghamohammadi A, Farhoudi A, Movahedi M, Gharagozlou M, et al. Consanguinity in primary immunodeficiency disorders; the report from Iranian Primary Immunodeficiency Registry. Am J Reprod Immunol. 2006;56(2):145-151. 26. Nissenkorn A, Levy-Shraga Y, Banet-Levi Y, Lahad A, Sarouk I, Modan-Moses D. Endocrine abnormalities in ataxia telangiectasia: findings from a national cohort. Pediatr. Res. 2016;79(6):889-94. 27. Boder E, Sedgwick RP. Ataxia-telangiectasia. (Clinical and immunological aspects). Psychiatr Neurol Med Psychol Beih. 1970;13-14:8-16. 28. Hoche F, Seidel K, Theis M, Vlaho S, Schubert R, Zielen S, et al. Neurodegeneration in ataxia telangiectasia: what is new? What is evident? Neuropediatrics. 2012;43(3):119-29. 29. Jozwiak S. Ataxia-Telangiectasia. Emedicine com. 2005;13. 30. Cabana MD, Crawford TO, Winkelstein JA, Christensen JR, Lederman HM. Consequences of the delayed diagnosis of ataxia-telangiectasia. Pediatrics. 1998;102(1 Pt 1):98-100. 31. Stray-Pedersen A, Borresen-Dale AL, Paus E, Lindman CR, Burgers T, Abrahamsen TG.Alpha fetoprotein is increasing with age in ataxia-telangiectasia. Eur J Paediatr Neurol. 2007;11(6):375-380. 32. Waldmann T. Immunological abnormalities in ataxia-telangiectasia. Ataxia-telangiectasia: A Cellar and Molecular Link between Cancer Neuropthology and Immune Deficiency. 1982. P. 37-51. 33. Ament M. Respiratory complications of ataxia-telangiectasia. N Engl J Med 1969;281(18):1019. 34. Bobba N, Kaplan MS. Immunodeficiency and Infections in Ataxia-Telangiectasia. Pediatrics. 2005;116(Supplement 2):568. 35.Buckley RH. Pulmonarycomplications of primary immunodeficiencies. Paediatr Respir Rev. 2004;5:S225-33. 36. Bott L, Lebreton J, Thumerelle C, Cuvellier J, Deschildre A, Sardet A. Lung disease in ataxia-telangiectasia. Acta Paediatr. 2007;96(7):1021-4. 37. Schalch DS, McFarlin DE, Barlow MH. An unusual form of diabetes mellitus in ataxia telangiectasia. N Engl J Med. 1970;282(25):1396-402. 38. Su Y, Swift M. Mortality rates among carriers of ataxia-telangiectasia mutant alleles. Annals of internal medicine. 2000;133(10):770-8. 39. Tangsinmankong N, Wayne AS, Howenstine MS, Washington KR, Langston C, Gatti RA, et al. Lymphocytic interstitial pneumonitis, elevated IgM concentration, and hepatosplenomegaly in ataxia-telangiectasia. J Pediatr. 2001;138(6):939-41. 40. Ghiasy S, Parvaneh L, Azizi G, Sadri G, Zaki Dizaji M, Abolhassani H, et al. The clinical significance of complete class switching defect in Ataxia telangiectasia patients. Expert Rev Clin Immunol. 2017;13(5):499-505. 41. Meyts I, Weemaes C, De Wolf-Peeters C, Proesmans M, Renard M, Uyttebroeck A, et al. Unusual and severe disease course in a child with ataxia-telangiectasia. Pediatr Allergy Immunol. 2003;14(4):330-3. 42. Azarsiz E, Karaca NE, Gunaydin NC, Gulez N, Ozturk C, Aksu G, et al. Do elevated serum IgM levels have to be included in probable diagnosis criteria of patients with ataxia- telangiectasia? Int J Immunopath Ph. 2014;27(3):421-7. 43. Razaghian A, Ziaee V, Momen T, Shariat M. Misclassification of Ataxia Telangiectasia with Hyper IgM Immune Profile. Immunol Gene J 2019;2(3):147-52. 44. Chrzanowska KH, Gregorek H, Dembowska- Baginska B, Kalina MA, Digweed M. Nijmegen breakage syndrome (NBS). Orphanet J Rare Dis 2012;7:pp.13. 45. Voss S, Pietzner J, Hoche F, Taylor AM, Last JI, Schubert R, et al. Growth retardation and growth hormone deficiency in patients with Ataxia telangiectasia. Growth Factors. 2014;32(3-4):123-129 46. Ehlayel M, Soliman A, De Sanctis V. Linear growth and endocrine function in children with ataxia telangiectasia. Indian J Endocrinol Metab. 2014;18(Suppl 1):S93-6. 47. Lewis RF, Lederman HM, Crawford TO. Ocular motor abnormalities in ataxia telangiectasia. Ann Neurol. 1999;46(3):287-95. 48. Shaikh AG, Marti S, Tarnutzer AA, Palla A, Crawford TO, Straumann D, et al. Ataxia telangiectasia: a “disease model” to understand the cerebellar control of vestibular reflexes. J Neurophysiol. 2011;105(6):3034-41. 49. Shaikh AG, Marti S, Tarnutzer AA, Palla A, Crawford TO, Straumann D, et al. Gaze fixation deficits and their implication in ataxia-telangiectasia. J Neurol Neurosurg Psychiatry. 2009;80(8):858-64. 50. Driessen GJ, Ijspeert H, Weemaes CM, Haraldsson A, Trip M, Warris A, et al. Antibody deficiency in patients with ataxia telangiectasia is caused by disturbed B- and T-cell homeostasisand reduced immune repertoire diversity. J Allergy Clin Immunol. 2013;131(5):1367-75.e9. 51.Mohammadinejad P, Abolhassani H, Aghamohammadi A, Pourhamdi S, Ghosh S, Sadeghi B, et al. Class switch recombination process in ataxia telangiectasia patients with elevated serum levels of IgM. J Immunoassay Immunochem. 2015;36(1):16-26. 52.Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM. Immunodeficiency and infections in ataxia- telangiectasia. J Pediatr. 2004;144(4):pp.505-11. 53. Crawford TO, Skolasky R, Fernandez R, Rosquist K, Lederman H. Survival probability in ataxia telangiectasia. Arch Dis Child. 2006;91(7):610-1. 54. Canny GJ, Roifman C, Weitzman S, Braudo M, Levison H. A pulmonary infiltrate in a child with ataxia telangiectasia. Ann Allergy1988;61(6):422-3,66-8.