title: New advances in the diagnosis and treatment of autoimmune lymphoproliferative syndrome.
abstract: OBJECTIVE
  Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of disrupted lymphocyte homeostasis, resulting from mutations in the Fas apoptotic pathway. Clinical manifestations include lymphadenopathy, splenomegaly, and autoimmune cytopenias. A number of new insights have improved the understanding of the genetics and biology of ALPS. These will be discussed in this review.
  
  
  RESULTS
  A number of key observations have been made recently that better define the pathophysiology of ALPS, including the characterization of somatic FAS variant ALPS, the identification of haploinsufficiency as a mechanism of decreased Fas expression, and the description of multiple genetic hits in FAS in some families that may explain the variable penetrance of the disease. In addition, ALPS has been shown to be a more common condition, as patients diagnosed with other disorders, including Evans syndrome and common variable immune deficiency, have been found to have ALPS. Finally, the treatment of the disease has changed as splenectomy and rituximab have been shown to have unexpected ALPS-specific toxicities, and mycophenolate mofetil and sirolimus have been demonstrated to have marked activity against the disease.
  
  
  CONCLUSIONS
  On the basis of novel advances, the diagnostic algorithm and recommended treatment for ALPS have changed significantly, improving quality of life for many patients.
authors.affiliation: Division of Pediatric Hematology, Children's Hospital of Philadelphia, University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania, USA. teacheyd@E-Mail.chop.edu
authors.forename: David T
authors.initials: DT
authors.lastname: Teachey
mesh_terms: D056735:Autoimmune Lymphoproliferative Syndrome / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008206:Lymphatic Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D015398:Signal Transduction; D020123:Sirolimus / Q000627:therapeutic use; D013163:Splenomegaly / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D019014:fas Receptor / Q000187:drug effects* / Q000235:genetics
chemical_list: C491901:FAS protein, human; D007166:Immunosuppressive Agents; D019014:fas Receptor; D009173:Mycophenolic Acid; D020123:Sirolimus