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Bruton Agammaglobulinemia Differential Diagnoses

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
Updated: Jun 08, 2016

Diagnostic Considerations

Also consider the following:

  • Lymphoproliferative disorders
  • T-cell disorders
  • Transient hypogammaglobulinemia of infancy
  • Growth hormone deficiency
  • X-linked deficiency with hyper immunoglobulin M (IgM)

Transient myelodysplastic syndrome has been described in X-linked agammaglobulinemia (XLA), or Bruton agammaglobulinemia, with a novel BTK mutation.[20]

Persons with XLA may be at increased risk of multiple colorectal neoplasms.[21]

An autoimmunity phenotype is less common in patients with XLA than in those with different types of primary antibody deficiency.[22]

Differential Diagnoses

Contributor Information and Disclosures

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.


Franklin Desposito, MD Professor of Pediatrics and Clinical Director, Center for Human and Molecular Genetics, Rutgers New Jersey Medical School; Consulting Staff, Department of Pediatrics, UMDNJ-University Hospital

Franklin Desposito, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Rosalie Elenitsas, MD Herman Beerman Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System

Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, American Society of Dermatopathology, Pennsylvania Academy of Dermatology

Disclosure: Received royalty from Lippincott Williams Wilkins for textbook editor.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Julie R Kenner, MD, PhD Private Practice, Kenner Dermatology Center

Julie R Kenner, MD, PhD is a member of the following medical societies: American Academy of Dermatology, American Society for Dermatologic Surgery

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author, Isabel N. Granja Jander, MD, to the development and writing of this article.

  1. Conley ME, Broides A, Hernandez-Trujillo V, et al. Genetic analysis of patients with defects in early B-cell development. Immunol Rev. 2005 Feb. 203:216-34. [Medline].

  2. Vihinen M, Kwan SP, Lester T, et al. Mutations of the human BTK gene coding for bruton tyrosine kinase in X-linked agammaglobulinemia. Hum Mutat. 1999. 13(4):280-5. [Medline].

  3. Vihinen M, Mattsson PT, Smith CI. Bruton tyrosine kinase (BTK) in X-linked agammaglobulinemia (XLA). Front Biosci. 2000 Dec 1. 5:D917-28. [Medline].

  4. Wang XC, Wang Y, Kanegane H, Toshio M, Yu YH. [Gene diagnosis of X-linked agammaglobulinemia]. Zhonghua Er Ke Za Zhi. 2005 Jun. 43(6):449-52. [Medline].

  5. Wang Y, Kanegane H, Sanal O, et al. Bruton tyrosine kinase gene mutations in Turkish patients with presumed X-linked agammaglobulinemia. Hum Mutat. 2001 Oct. 18(4):356. [Medline].

  6. Khan WN. Regulation of B lymphocyte development and activation by Bruton's tyrosine kinase. Immunol Res. 2001. 23(2-3):147-56. [Medline].

  7. Ng YS, Wardemann H, Chelnis J, Cunningham-Rundles C, Meffre E. Bruton's tyrosine kinase is essential for human B cell tolerance. J Exp Med. 2004 Oct 4. 200(7):927-34. [Medline].

  8. Satterthwaite AB, Witte ON. The role of Bruton's tyrosine kinase in B-cell development and function: a genetic perspective. Immunol Rev. 2000 Jun. 175:120-7. [Medline].

  9. Poizeau F, Droitcourt C, Saillard C, Poirot M, Le Gallou T, Perlat A, et al. [Shifting cellulitis in a patient with X-linked hypogammaglobulinemia]. Ann Dermatol Venereol. 2016 Apr 11. [Medline].

  10. Giorgetti OB, Paolini MV, Oleastro MM, Fernández Romero DS. [X-linked agammaglobulinemia in adults. Clinical evolution]. Medicina (B Aires). 2016. 76 (2):65-70. [Medline].

  11. Chun JK, Lee TJ, Song JW, Linton JA, Kim DS. Analysis of clinical presentations of Bruton disease: a review of 20 years of accumulated data from pediatric patients at Severance Hospital. Yonsei Med J. 2008 Feb 29. 49(1):28-36. [Medline].

  12. Futatani T, Watanabe C, Baba Y, Tsukada S, Ochs HD. Bruton's tyrosine kinase is present in normal platelets and its absence identifies patients with X-linked agammaglobulinaemia and carrier females. Br J Haematol. 2001 Jul. 114(1):141-9. [Medline].

  13. Speletas M, Kanariou M, Kanakoudi-Tsakalidou F, et al. Analysis of Btk mutations in patients with X-linked agammaglobulinaemia (XLA) and determination of carrier status in normal female relatives: a nationwide study of Btk deficiency in Greece. Scand J Immunol. 2001 Sep. 54(3):321-7. [Medline].

  14. Chear CT, Ripen AM, Mohamed SA, Dhaliwal JS. A novel BTK gene mutation creates a de-novo splice site in an X-linked agammaglobulinemia patient. Gene. 2015 Apr 15. 560 (2):245-8. [Medline].

  15. Ariganello P, Angelino G, Scarselli A, Salfa I, Della Corte M, De Matteis A, et al. Relapsing Campylobacter jejuni Systemic Infections in a Child with X-Linked Agammaglobulinemia. Case Rep Pediatr. 2013. 2013:735108. [Medline]. [Full Text].

  16. Fu JL, Shyur SD, Lin HY, Lai YC. X-linked agammaglobulinemia presenting as juvenile chronic arthritis: report of one case. Acta Paediatr Taiwan. 1999 Jul-Aug. 40(4):280-3. [Medline].

  17. Quartier P, Foray S, Casanova JL, Hau-Rainsard I, Blanche S, Fischer A. Enteroviral meningoencephalitis in X-linked agammaglobulinemia: intensive immunoglobulin therapy and sequential viral detection in cerebrospinal fluid by polymerase chain reaction. Pediatr Infect Dis J. 2000 Nov. 19(11):1106-8. [Medline].

  18. Vu QV, Wada T, Le HT, Le HT, Van Nguyen AT, Osamu O, et al. Clinical and mutational features of Vietnamese children with X-linked agammaglobulinemia. BMC Pediatr. 2014 May 28. 14:129. [Medline]. [Full Text].

  19. Murray PR, Jain A, Uzel G, Ranken R, Ivy C, Blyn LB, et al. Pyoderma gangrenosum-like ulcer in a patient with X-linked agammaglobulinemia: identification of Helicobacter bilis by mass spectrometry analysis. Arch Dermatol. 2010 May. 146(5):523-6. [Medline].

  20. Narula G, Currimbhoy Z. Transient myelodysplastic syndrome in X-linked agammaglobulinemia with a novel Btk mutation. Pediatr Blood Cancer. 2008 Dec. 51(6):826-8. [Medline].

  21. Brosens LA, Tytgat KM, Morsink FH, et al. Multiple colorectal neoplasms in X-linked agammaglobulinemia. Clin Gastroenterol Hepatol. 2008 Jan. 6(1):115-9. [Medline].

  22. Behniafard N, Aghamohammadi A, Abolhassani H, Pourjabbar S, Sabouni F, Rezaei N. Autoimmunity in X-linked agammaglobulinemia: Kawasaki disease and review of the literature. Expert Rev Clin Immunol. 2012 Feb. 8(2):155-9. [Medline].

  23. Qin X, Jiang LP, Tang XM, Wang M, Liu EM, Zhao XD. Clinical features and mutation analysis of X-linked agammaglobulinemia in 20 Chinese patients. World J Pediatr. 2013 Jan 18. [Medline].

  24. D'Eufemia P, Nigro G, Celli M, Finocchiaro R, Iannetti P, Giardini O. Low-dosage immunoglobulins for an infant with hypogammaglobulinemia, maple syrup urine disease, and parvovirus B19-associated aplastic crisis. J Pediatr Hematol Oncol. 2000 Sep-Oct. 22(5):485-7. [Medline].

  25. Eijkhout HW, van Der Meer JW, Kallenberg CG, et al. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med. 2001 Aug 7. 135(3):165-74. [Medline].

  26. Davey PT, Tan CJ, Gardiner K. The use of infliximab in X-linked agammaglobulinaemia associated enteropathy. Ann R Coll Surg Engl. 2014 Jul. 96(5):e5-6. [Medline].

  27. Hendriks RW, Bredius RG, Pike-Overzet K, Staal FJ. Biology and novel treatment options for XLA, the most common monogenetic immunodeficiency in man. Expert Opin Ther Targets. 2011 Aug. 15(8):1003-21. [Medline].

  28. Bestas B, Turunen JJ, Blomberg KE, Wang Q, Månsson R, El Andaloussi S, et al. Splice-correction strategies for treatment of X-linked agammaglobulinemia. Curr Allergy Asthma Rep. 2015 Mar. 15 (3):510. [Medline].

  29. Park JY, Kim YS, Shin DH, Choi JS, Kim KH, Bae YK. Primary cutaneous peripheral T-cell lymphoma in a patient with X-linked agammaglobulinaemia. Br J Dermatol. 2011 Mar. 164(3):677-9. [Medline].

  30. Lee KH, Shyur SD, Chu SH, Huang LH, Kao YH, Lei WT, et al. Clinical manifestations and BTK gene defect in 4 unrelated Taiwanese families with Bruton's disease. Asian Pac J Allergy Immunol. 2011 Sep. 29(3):260-5. [Medline].

Early stages of B-cell differentiation can be identified by the status of the immunoglobulin genes and by the cell surface markers CD34, CD19, and surface immunoglobulin (sIg). From: Conley ME. Genes required for B cell development. J Clin Invest. 2003;112: 1636-8. Reproduced with permission of American Society for Clinical Investigation via Copyright Clearance Center.
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