title: Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience.
abstract: BACKGROUND
  The approach to the diagnosis of severe combined immunodeficiency disease (SCID) and related disorders varies among institutions and countries.
  
  
  OBJECTIVE
  The Primary Immune Deficiency Treatment Consortium attempted to develop a uniform set of criteria for diagnosing SCID and related disorders and has evaluated the results as part of a retrospective study of SCID in North America.
  
  
  METHODS
  Clinical records from 2000 through 2009 at 27 centers in North America were collected on 332 children treated with hematopoietic stem cell transplantation (HCT), enzyme replacement therapy, or gene therapy for SCID and related disorders. Eligibility for inclusion in the study and classification into disease groups were established by using set criteria and applied by an expert review group.
  
  
  RESULTS
  Two hundred eighty-five (86%) of the patients were determined to be eligible, and 47 (14%) were not eligible. Of the 285 eligible patients, 84% were classified as having typical SCID; 13% were classified as having leaky SCID, Omenn syndrome, or reticular dysgenesis; and 3% had a history of enzyme replacement or gene therapy. Detection of a genotype predicting an SCID phenotype was accepted for eligibility. Reasons for noneligibility were failure to demonstrate either impaired lymphocyte proliferation or maternal T-cell engraftment. Overall (n = 332) rates of testing were as follows: proliferation to PHA, 77%; maternal engraftment, 35%; and genotype, 79% (mutation identified in 62%).
  
  
  CONCLUSIONS
  Lack of complete laboratory evaluation of patients before HCT presents a significant barrier to definitive diagnosis of SCID and related disorders and prevented inclusion of subjects in our observational HCT study. This lesson is critical for patient care, as well as the design of future prospective treatment studies for such children because a well-defined and consistent study population is important for precision in outcomes analysis.
authors.affiliation: Department of Pediatrics, Section of Immunology, Allergy, and Rheumatology, Baylor College of Medicine, Texas Children's Hospital, Houston, Tex. Electronic address: wtshearer@texaschildrens.org.
authors.forename: William T
authors.initials: WT
authors.lastname: Shearer
authors.affiliation: Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplant, Benioff Children's Hospital, University of California San Francisco, San Francisco, Calif.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dunn
authors.affiliation: Division of Biostatistics, Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wis.
authors.forename: Luigi D
authors.initials: LD
authors.lastname: Notarangelo
authors.affiliation: Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplant, Benioff Children's Hospital, University of California San Francisco, San Francisco, Calif.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Dvorak
authors.affiliation: Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplant, Benioff Children's Hospital, University of California San Francisco, San Francisco, Calif.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Puck
authors.affiliation: Division of Immunology and the Manton Center for Orphan Disease Research, Children's Hospital Boston, and Harvard Stem Cell Institute, Harvard Medical School, Boston, Mass.
authors.forename: Brent R
authors.initials: BR
authors.lastname: Logan
authors.affiliation: Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
authors.forename: Linda M
authors.initials: LM
authors.lastname: Griffith
authors.affiliation: Departments of Microbiology, Immunology & Molecular Genetics and Pediatrics, University of California, Los Angeles, Calif.
authors.forename: Donald B
authors.initials: DB
authors.lastname: Kohn
authors.affiliation: Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: O'Reilly
authors.affiliation: Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, Md.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Fleisher
authors.affiliation: Division of Hematology and Oncology, Boston Children's Hospital, and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Mass.
authors.forename: Sung-Yun
authors.initials: SY
authors.lastname: Pai
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital Cancer Center, Houston, Tex.
authors.forename: Caridad A
authors.initials: CA
authors.lastname: Martinez
authors.affiliation: Department of Pediatrics and Immunology, Duke University Medical Center, Durham, NC.
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Buckley
authors.affiliation: Division of Pediatric Allergy, Immunology, and Blood and Marrow Transplant, Benioff Children's Hospital, University of California San Francisco, San Francisco, Calif.
authors.forename: Morton J
authors.initials: MJ
authors.lastname: Cowan
mesh_terms: D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000175:diagnosis; D009656:North America; D017410:Practice Guidelines as Topic; D012189:Retrospective Studies; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis*
keywords: Allogeneic hematopoietic cell transplantation; clinical trial; gene therapy; primary immunodeficiency