FaCD Online Syndrome Fact Sheet

Last updated: 17 May 2010

Name: Agammaglobulinemia, X-linked

Synonym: Bruton Type Agammaglobulinemia

Mode of Inheritance: XLR

Genes

BTK, mapped to Xq21.3-q22

Tumor features

colorectal cancer
Hodgkin disease (Hodgkin's lymphoma)
leukemia, acute lymphoblastic (ALL)
leukemia, chronic myeloid (CML)
non-Hodgkin lymphoma
thymoma

Tumor features (possible)

gastric cancer
lung/bronchial cancer

Non-tumor features

agammaglobulinemia
immunodeficiency

Comment

This infantile immunodeficiency in males is characterized by an isolated B-cell defect and these cells are absent in the vast majority of patients. Lymphoid tissue (adenoid, tonsils) is either absent or hypoplastic[15] and infection is usually the first presenting symptom[17]. There is approximately an incidence of 1.5-6 % of malignancies in this disorder, mainly involving the hematopoietic-lymphoid system[1-9]. Patients also have an increased risk to develop colorectal cancer as early as in their 20s [10,11]. However, the exact level of colorectal cancer risk is still unclear[17]. Other tumors have been reported as well: lung cancer was diagnosed in a 32 year-old nonsmoking male[12], liver cancer[16] and gastric cancer associated with chronic atrophic gastritis[13,14].

References

[1] Penn I. Occurrence of cancer in immune deficiencies. Cancer 1974; 34(3):suppl:858-66.
[2] Gatti RA, Good RA. Occurrence of malignancy in immunodeficiency diseases. A literature review. Cancer 1971; 28(1):89-98.
[3] Van der Meer JW, Zegers BJ. Agammaglobulinaemia. Neth J Med 1994; 45(6):250-256.
[4] Filipovich AH, Spector BD, Kersey J. Immunodeficiency in humans as a risk factor in the development of malignancy. Prev Med 1980; 9:252-259.
[5] Lederman HM. Cancer in children with primary or secondary immunodeficiencies [letter; comment]. J Pediat 1995; 127(2):335.
[6] Page AR, Hansen AE, Good RA. Occurrence of leukemia and lymphoma in patients with agammaglobulinemia. Blood 1963; 21(2):197-206.
[7] Mueller BU, Pizzo PA. Cancer in children with primary or secondary immunodeficiencies. J Pediat 1995; 126(1):1-10.
[8] Spector BD, Perry GS, Kersey JH. Genetically determined immunodeficiency diseases (GDID) and malignancy: report from the immunodefciency-cancer registry. Clin Immunol Immunopathol 1978; 11:12-29.
[9] Kersey JH, Spector BD, Good RA. Primary immunodeficiency diseases and cancer: the immunodeficiency-cancer registry. Int J Cancer 1973; 12(2):333-347.
[10] Van der Meer JW, Weening RS, Schellekens PT, van Munster IP, Nagengast FM. Colorectal cancer in patients with X-linked agammaglobulinaemia. Lancet 1993; 341(8858):1439-1440.
[11] Brosens LA, Tytgat KM, Morsink FH, Sinke RJ, Ten Berge IJ, Giardiello FM, Offerhaus GJ, Keller JJ. Multiple colorectal neoplasms in X-linked agammaglobulinemia. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2008; 6(1):115-9.
[12] Echave-Sustaeta JM, Villena V, Verdugo M, López-Encuentra A, de Agustín P, Alberti N. X-linked agammaglobulinaemia and squamous lung cancer. The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology 2001; 17(3):570-2.
[13] Bachmeyer C, Monge M, Cazier A, Le Deist F, de Saint Basile G, Durandy A, Fischer A, Mougeot-Martin M. Gastric adenocarcinoma in a patient with X-linked agammaglobulinaemia. European journal of gastroenterology & hepatology 2000; 12(9):1033-5.
[14] Lavilla P, Gil A, Rodríguez MC, Dupla ML, Pintado V, Fontán G. X-linked agammaglobulinemia and gastric adenocarcinoma. Cancer 1993; 72(5):1528-31.
[15] Lee PP, Chen TX, Jiang LP, Chan KW, Yang W, Lee BW, Chiang WC, Chen XY, Fok SF, Lee TL, Ho MH, Yang XQ, Lau YL. Clinical characteristics and genotype-phenotype correlation in 62 patients with X-linked agammaglobulinemia. J Clin Immunol. 2010 Jan;30(1):121-31.
[16] Wang Y, Kanegane H, Wang X, Han X, Zhang Q, Zhao S, Yu Y, Wang J, Miyawaki T. Mutation of the BTK gene and clinical feature of X-linked agammaglobulinemia in mainland China. J Clin Immunol. 2009 May;29(3):352-6.
[17] Winkelstein JA, Marino MC, Lederman HM, Jones SM, Sullivan K, Burks AW, Conley ME, Cunningham-Rundles C, Ochs HD. X-linked agammaglobulinemia: report on a United States registry of 201 patients. Medicine (Baltimore). 2006 Jul;85(4):193-202.