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

Eur J Haematol. 2007 Oct;79(4):363-6. doi: 10.1111/j.1600-0609.2007.00924.x. Epub 2007 Aug 28.

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.

Publication types

  • Case Reports

MeSH terms

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

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antineoplastic Agents
  • RNA Splice Sites
  • fas Receptor
  • Rituximab