title: Clinical and immunological manifestations of patients with atypical severe combined immunodeficiency.
abstract: Hypomorphic mutations in genes associated with severe combined immunodeficiency (SCID) or Omenn syndrome can also cause milder immunodeficiencies. We report 10 new patients with such "atypical" SCID and summarize 63 patients from the literature. The patient groups with T(low)B(low) (n=28), T(low)B(+) (n=16) and ADA (n=29) SCID variants had similar infection profiles but differed in the frequency of immune dysregulation, which was observed predominantly in patients with recombination defects. Most immunological parameters were remarkably similar in the three groups. Of note, 19/68 patients with "atypical" SCID had normal T cell counts, 48/68 had normal IgG and 23/46 had at least one normal specific antibody titer. Elevated IgE was a characteristic feature of ADA deficiency. This overview characterizes "atypical" SCID as a distinct disease with immune dysregulation in addition to infection susceptibility. Lymphopenia, reduced naïve T cells and elevated IgE are suggestive, but not consistent features of the disease.
authors.affiliation: Centre of Chronic Immunodeficiency, University Hospital Freiburg, Breisacher Str. 117, D-79106 Freiburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Felgentreff
authors.forename: Ruy
authors.initials: R
authors.lastname: Perez-Becker
authors.forename: Carsten
authors.initials: C
authors.lastname: Speckmann
authors.forename: Klaus
authors.initials: K
authors.lastname: Schwarz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Kalwak
authors.forename: Gasper
authors.initials: G
authors.lastname: Markelj
authors.forename: Tadej
authors.initials: T
authors.lastname: Avcin
authors.forename: Waseem
authors.initials: W
authors.lastname: Qasim
authors.forename: E G
authors.initials: EG
authors.lastname: Davies
authors.forename: Tim
authors.initials: T
authors.lastname: Niehues
authors.forename: Stephan
authors.initials: S
authors.lastname: Ehl
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000150:complications / Q000235:genetics / Q000276:immunology; D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007231:Infant, Newborn; D007239:Infections / Q000209:etiology; D009154:Mutation; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D007073:Immunoglobulin E; D000243:Adenosine Deaminase