title: From Severe Combined Immunodeficiency to Omenn syndrome after hematopoietic stem cell transplantation in a RAG1 deficient family.
abstract: BACKGROUND
  Mutations in RAG genes cause a spectrum of severe immunodeficiencies ranging from Severe Combined Immunodeficiency (SCID) T-B-NK+ to Omenn syndrome (OS) through intermediate phenotypes, even for the same alteration. Nowadays, hematopoietic stem cell transplantation (HSCT) is the unique curative treatment available.
  
  
  METHODS
  We describe three related patients from a Moroccan consanguineous family. Patient 1 developed at 1 month of age moderate eczematous dermatitis with eosinophilia, followed by infections and enteritis. He was transplanted and received reduced intensity conditioning regimen previous to HSCT. His brother, patient 2, was born preterm with a severe neonatal erythroderma, hepatosplenomegaly and lymphadenopathy. Patient 3, cousin of the two siblings, was also born preterm and fulfilled all criteria for classical OS. Immunological evaluation was performed and RAG genes were sequenced.
  
  
  RESULTS
  Immunological data from all three patients were very diversed, from T lymphopenia to marked lymphocytosis, and different degrees of eosinophilia and IgE levels. Non-responder T cells and absent B cells were constant. All patients presented the same homozygous mutation in RAG1 gene (c.631delT). Patient 1 fully recovered both clinically and immunologically after HSCT. Two years later, he lost the accomplished lymphoid chimera and the disease relapsed as a classical OS, leading to patient's death.
  
  
  CONCLUSIONS
  This is the first report of a RAG1 deficient patient with a changed clinical and immunological phenotype from SCID to OS after HSCT. The use of a myeloablative conditioning regimen that eliminates reminiscent T cells might have improved patient's outcome and it should be considered in similar cases.
authors.affiliation: Immunology, Hospital de la Santa Creu i Sant Pau, Universitat Autónoma de Barcelona, Pare Claret, Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Martinez-Martinez
authors.forename: Marta
authors.initials: M
authors.lastname: Vazquez-Ortiz
authors.forename: Cecilia
authors.initials: C
authors.lastname: Gonzalez-Santesteban
authors.forename: Andrea
authors.initials: A
authors.lastname: Martin-Nalda
authors.forename: Asunción
authors.initials: A
authors.lastname: Vicente
authors.forename: Ana M
authors.initials: AM
authors.lastname: Plaza
authors.forename: Isabel
authors.initials: I
authors.lastname: Badell
authors.forename: Laia
authors.initials: L
authors.lastname: Alsina
authors.forename: Oscar
authors.initials: O
authors.lastname: de la Calle-Martin
mesh_terms: D046528:Chimerism; D003241:Consanguinity; D004252:DNA Mutational Analysis; D004485:Eczema / Q000209:etiology / Q000235:genetics* / Q000517:prevention & control; D004751:Enteritis / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D017809:Fatal Outcome; D018380:Hematopoietic Stem Cell Transplantation; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009018:Morocco; D010375:Pedigree; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000235:genetics* / Q000628:therapy
chemical_list: D018398:Homeodomain Proteins; C064658:RAG-1 protein