FaCD Online Syndrome Fact Sheet

Last updated: 06 Feb 2008

Name: Autoimmune Lymphoproliferative syndrome, type I

Synonym: Canale-Smith syndrome, ALPS type I (incl.: ALPS1A, ALPS1B), incl. Autoimmune Lymphoproliferative Disease (ALD)

Mode of Inheritance: AD

Genes

APT1/FAS, mapped to 10q24.1

Tumor features

Burkitt lymphoma
Hodgkin disease (Hodgkin's lymphoma)
non-Hodgkin lymphoma

Tumor features (possible)

hepatocellular cancer (hepatoma)

Non-tumor features

autoimmune disease

Comment

This disorder develops in early childhood because of a defective lymphocyte apoptosis. It is characterized by non-malignant lymphadenopathy, splenomegaly and autoimmune disease.[1]. In the majority of patients a heterozygous mutation in APT1 has been detected. APT1 encodes the Fas protein, which is a mediator of lymphocyte apoptosis.
Of 46 ALPS1 patients with APT1 mutations studied at the NIH, 6 (13 %) developed a lymphoma: Hodgkin, Burkitt, follicular lymphoma or non-Hodgkin lymphoma[2,3]. A case of hepatocellular carcinoma has also been reported. In general, risk for non-Hodgkin lymphoma and Hodgkins disease is increased.

Ramenghi et al.[4] reported an ALPS-like disorder, which they referred to as autoimmune lymphoproliferative disease (ALD), associated with decreased Fas function in the absence of detectable Fas mutations. Hodgkin disease was reported by them to have occurred in one of these ALD families and the frequency of cancer in general was increased in the families’ maternal lines.

References

[1] Straus SE, Sneller M, Lenardo MJ, Puck JM, Strober W. An inherited disorder of lymphocyte apoptosis: the autoimmune lymphoproliferative syndrome. Ann Intern Med 1999; 130(7):591-601.
[2] Jackson CE, Wang J, Fischer RE, Hsu AP, Niemela J, Dale JK, Fleischer TA, Jaffe ES, Lenardo MJ, Straus SE, Puck JM. Autoimmune lymphoproliferative syndrome (ALPS): an disorder of aptosis with predisposition to development of diverse lymphomas. Am J Hum Genet 65[4], A48. 1999.
[3] Rao VK, Straus SE. Causes and consequences of the autoimmune lymphoproliferative syndrome. Hematology (Amsterdam, Netherlands) 2006; 11(1):15-23.
[4] Ramenghi U, Bonissoni S, Migliaretti G, DeFranco S, Bottarel F, Gambaruto C, DiFranco D, Priori R, Conti F, Dianzani I, Valesini G, Merletti F, Dianzani U. Deficiency of the Fas apoptosis pathway without Fas gene mutations is a familial trait predisposing to development of autoimmune diseases and cancer. Blood 2000; 95(10):3176-3182.