FaCD Online Syndrome Fact Sheet

Last updated: 23 Jun 2008

Name: Immune Deficiency with Hyper-IgM

Synonym: Hypogammaglobulinemia with Hyper-IgM, HIGM type I-V, XLHIGM

Mode of Inheritance: XL / AR

Genes

AID, mapped to 12p13
CD40, mapped to 20q12-q13.2
CD40LG, mapped to Xq26
UNG, mapped to 12q23-q24.1

Tumor features (possible)

biliary tract cancer (incl. gallbladder)
colorectal neuroendocrine tumor
hepatocellular cancer (hepatoma)
Hodgkin disease (Hodgkin's lymphoma)
Kaposi sarcoma
non-Hodgkin lymphoma
pancreatic endocrine tumor

Non-tumor features

high IgM and low IgA and IgG
immunodeficiency

Comment

This entry summarizes a group of disorders characterized by normal or elevated IgM in the presence of diminished IgG and IgA levels. Approximately 70 % of cases are X-linked and in those cases, affected males suffer from recurrent pyogenic infections (especially with P. Carinii). Patients may suffer from extensive proliferation of IgM-producing polyclonal plasma cells, involving the gastrointestinal tract and hepatobiliary system, which may be fatal.[1].

Hodgkin disease and Non Hodgkin lymphoma have been reported in patients with hyper-IgM syndrome[2,3]. Other tumors that have been observed include neuroendocrine pancreatic tumors [5,6], large cell lymphocytic leukemia which is a NHL subtype[7], Kaposi sarcoma[8], hepatocellular cancer[9,12], biliary tract cancer[11] and oat cell, neuroendocrine, tumor of the colon[12 ]

Hamoudi et al.[4] reported a girl who developed multiple adenomatous polyps in her colon, 1 of them malignant, at the age of 10 years, after which she developed over a period of 8 years a malignant thymoma, squamous cell cancer of the scalp, colon cancer, choroidal tumor, finally dying at the age of 20 years from a brain tumor (astrocytoma). She had low Ig A and IgG2 levels, normal IgM and total IgG. Her brother had a total absence of IgA, low IgG and high IgM and died at the age of 16 from a lymphocytic lymphoma. Although this family was reported with an emphasis on the IgA deficiency, there was no selective IgA deficiency and possibly this family suffered from (a variant of) Hyper-IgM syndrome.

Links

International Patient Organisation for Primary Immunodeficiencies (IPOPI) 18 1 08

References

[1] Elenitoba-Johnson KS, Jaffe ES. Lymphoproliferative disorders associated with congenital immunodeficiencies. Semin Diagn Pathol 1997; 14(1):35-47.
[2] 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.
[3] Filipovich AH, Mathur A, Kamat D, Kersey JH, Shapiro RS. Lymphoproliferative disorders and other tumors complicating immunodeficiencies. Immunodeficiency 1994; 5(2):91-112.
[4] Hamoudi AB, Ertel I, Newton WA, Jr., Reiner CB, Clatworthy HW, Jr. Multiple neoplasms in an adolescent child associated with IGA deficiency. Cancer 1974; 33(4):1134-1144.
[5] Malhotra RK, Li W. Poorly differentiated gastroenteropancreatic neuroendocrine carcinoma associated with X-linked hyperimmunoglobulin M syndrome. Archives of pathology & laboratory medicine 2008; 132(5):847-50.
[6] Nagaraj N, Egwim C, Adler DG. X-linked hyper-IgM syndrome associated with poorly differentiated neuroendocrine tumor presenting as obstructive jaundice secondary to extensive adenopathy. Digestive diseases and sciences 2007; 52(9):2312-6.
[7] Kitchen BJ, Boxer LA. Large granular lymphocyte leukemia (LGL) in a child with hyper IgM syndrome and autoimmune hemolytic anemia. Pediatric blood & cancer 2008; 50(1):142-5.
[8] Nagasawa M, Itoh S, Sawada Y, Morio T, Nonoyama S, Mizutani S. Coagulopathy in a patient with X-linked hyper-IgM syndrome who developed Kaposi's sarcoma. American journal of hematology 2004; 75(2):116-7.
[9] Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, Stiehm ER, Conley ME. The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. Medicine 2003; 82(6):373-84.
[10] Rodríguez C, Carrión F, Marinovic MA, Chávez E, Preisler J, Pooley F, Futatani T, Ochs HD. [X-linked hyper-IGM syndrome associated to sclerosing cholangitis and gallbladder neoplasm: clinical case]. Revista médica de Chile 2003; 131(3):303-8.
[11] Hayward AR, Levy J, Facchetti F, Notarangelo L, Ochs HD, Etzioni A, Bonnefoy JY, Cosyns M, Weinberg A. Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM. Journal of immunology (Baltimore, Md. : 1950) 1997; 158(2):977-83.
[12] Zirkin HJ, Levy J, Katchko L. Small cell undifferentiated carcinoma of the colon associated with hepatocellular carcinoma in an immunodeficient patient. Human pathology 1996; 27(9):992-6.