Canale Smith syndrome

Canale Smith syndrome

Canale–Smith syndrome (autoimmune lymphoproliferative syndrome): a rare autosomal dominant disorder typically presenting in childhood and characterized by generalized lymphadenopathy, hepatosplenomegaly, and autoimmune hemolytic anemia and thrombocytopenia. Other organs (neurologic, lung, kidney, skin, etc.) can also be involved. Rarely patients with mutations causing a milder phenotype may not have symptoms until adulthood. Patients are diagnosed by increased numbers (≥5% of all T cells) of circulating double-negative T cells (CD3 + , CD4–, CD8–) which comprise >1.5% of all circulating lymphocytes. Most (70%) patients have germline mutations in the Fas gene ( TNFRSF6 ), leading to abnormalities in the intracellular “death domain” of the receptor Fas (APO-1, CD95). This leads to the inability of the T cell to be signaled to undergo programmed cell death (apoptosis). Consequently, autoreactive T cells will downregulate CD4 and CD8 molecules but cannot be disposed of by Fas-mediated apoptosis (similar to lpr mice), leading to autoimmune disease. Patients without Fas gene mutations have been found to have mutations in the Fas ligand gene (similar to gld mice) or enzymes involved in apoptosis (caspase 10, caspase 8). Corticosteroid therapy has variable effects. Mycophenolate mofetil and sirolimus have been effective steroid-sparing medications. Notably, up to 10% of patients can develop neoplasms (lymphoma).


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