title: Rituximab responsive immune thrombocytopenic purpura in an adult with underlying autoimmune lymphoproliferative syndrome due to a splice-site mutation (IVS7+2 T>C) affecting the Fas gene.
abstract: A 36 yr-old man of Israeli descent with a history of childhood splenectomy for severe thrombocytopenia and a family history of autoimmune lymphoproliferative syndrome (ALPS), presented with severe immune thrombocytopenic purpura refractory to standard therapy. He was found to possess a heterozygous mutation in the Fas gene (also termed TNFRSF6, CD95, Apo-1) affecting the donor splice site of intron 7 (IVS7+2 T>C). This frameshift mutation truncates the cytoplasmic domain of the Fas death receptor, resulting in circulating CD4/8 double negative T lymphocytes, lymphadenopathy and autoimmune complications typical of ALPS. Administration of Rituximab in this patient was associated with a durable hematologic response (currently more than 12 months). This report highlights the need to consider rare inherited causes of thrombocytopenia in adults with a family history of immune cytopenia(s) and the effective use of anti-CD20 monoclonal antibody in patients unresponsive to immunosuppression and splenectomy.
authors.affiliation: Haematology Department, St. Vincent's Hospital, 41 Victorial Parade, Fitzroy, Victoria, Australia. andrew.wei@svhm.org.au
authors.forename: Andrew
authors.initials: A
authors.lastname: Wei
authors.forename: Tiffany
authors.initials: T
authors.lastname: Cowie
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D030342:Genetic Diseases, Inborn / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy; D018655:Lymphocyte Count; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D008297:Male; D017354:Point Mutation; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D022821:RNA Splice Sites / Q000235:genetics*; D000069283:Rituximab; D013156:Splenectomy; D019014:fas Receptor / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D022821:RNA Splice Sites; D019014:fas Receptor; D000069283:Rituximab