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.
MeSH terms
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Adult
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Antibodies, Monoclonal / administration & dosage*
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Antibodies, Monoclonal, Murine-Derived
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Antineoplastic Agents / administration & dosage*
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Genetic Diseases, Inborn / blood
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Genetic Diseases, Inborn / complications
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Genetic Diseases, Inborn / drug therapy*
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Genetic Diseases, Inborn / genetics
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Genetic Diseases, Inborn / immunology
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Humans
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Immunosuppression Therapy
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Lymphocyte Count
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Lymphoproliferative Disorders / blood
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Lymphoproliferative Disorders / complications
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Lymphoproliferative Disorders / drug therapy*
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Lymphoproliferative Disorders / genetics
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Lymphoproliferative Disorders / immunology
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Male
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Point Mutation*
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Purpura, Thrombocytopenic, Idiopathic / blood
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Purpura, Thrombocytopenic, Idiopathic / complications
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Purpura, Thrombocytopenic, Idiopathic / drug therapy*
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Purpura, Thrombocytopenic, Idiopathic / genetics
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Purpura, Thrombocytopenic, Idiopathic / immunology
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RNA Splice Sites / genetics*
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Rituximab
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Splenectomy
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fas Receptor / genetics*
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fas Receptor / immunology
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fas Receptor / metabolism
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Murine-Derived
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Antineoplastic Agents
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RNA Splice Sites
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fas Receptor
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Rituximab