title: Tandem mass spectrometry, but not T-cell receptor excision circle analysis, identifies newborns with late-onset adenosine deaminase deficiency.
abstract: BACKGROUND
  Adenosine deaminase (ADA)-severe combined immunodeficiency (SCID) is caused by genetic variants that disrupt the function of ADA. In its early-onset form, it is rapidly fatal to infants. Delayed or late-onset ADA-SCID is characterized by insidious progressive immunodeficiency that leads to permanent organ damage or death. Quantification of T-cell receptor excision circles (TRECs) or tandem mass spectrometry (tandem-MS) analysis of dried blood spots (DBSs) collected at birth can identify newborns with early-onset ADA-SCID and are used in screening programs. However, it is not clear whether these analyses can identify newborns who will have delayed or late-onset ADA-SCID before symptoms appear.
  
  
  OBJECTIVE
  We performed a retrospective study to evaluate whether tandem-MS and quantitative TREC analyses of DBSs could identify newborns who had delayed-onset ADA-SCID later in life.
  
  
  METHODS
  We tested stored DBSs collected at birth from 3 patients with delayed-onset ADA-SCID using tandem-MS (PCT EP2010/070517) to evaluate levels of adenosine and 2'-deoxyadenosine and real-time PCR to quantify TREC levels. We also analyzed DBSs from 3 newborns with early-onset ADA-SCID and 2 healthy newborn carriers of ADA deficiency.
  
  
  RESULTS
  The DBSs taken at birth from the 3 patients with delayed-onset ADA-SCID had adenosine levels of 10, 25, and 19 μmol/L (normal value, <1.5 μmol/L) and 2'-deoxyadenosine levels of 0.7, 2.7, and 2.4 μmol/L (normal value, <0.07 μmol/L); the mean levels of adenosine and 2'-deoxyadenosine were respectively 12.0- and 27.6-fold higher than normal values. DBSs taken at birth from all 3 patients with delayed-onset ADA deficiency had normal TREC levels, but TRECs were undetectable in blood samples taken from the same patients at the time of diagnosis.
  
  
  CONCLUSIONS
  Tandem-MS but not TREC quantification identifies newborns with delayed- or late-onset ADA deficiency.
authors.affiliation: Department of Pharmacology, University of Florence, Florence, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: la Marca
authors.forename: Clementina
authors.initials: C
authors.lastname: Canessa
authors.forename: Elisa
authors.initials: E
authors.lastname: Giocaliere
authors.forename: Francesca
authors.initials: F
authors.lastname: Romano
authors.forename: Marzia
authors.initials: M
authors.lastname: Duse
authors.forename: Sabrina
authors.initials: S
authors.lastname: Malvagia
authors.forename: Francesca
authors.initials: F
authors.lastname: Lippi
authors.forename: Silvia
authors.initials: S
authors.lastname: Funghini
authors.forename: Leila
authors.initials: L
authors.lastname: Bianchi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Della Bona
authors.forename: Claudia
authors.initials: C
authors.lastname: Valleriani
authors.forename: Daniela
authors.initials: D
authors.lastname: Ombrone
authors.forename: Maria
authors.initials: M
authors.lastname: Moriondo
authors.forename: Fabio
authors.initials: F
authors.lastname: Villanelli
authors.forename: Carsten
authors.initials: C
authors.lastname: Speckmann
authors.forename: Stuart
authors.initials: S
authors.lastname: Adams
authors.forename: Bobby H
authors.initials: BH
authors.lastname: Gaspar
authors.forename: Michael
authors.initials: M
authors.lastname: Hershfield
authors.forename: Ines
authors.initials: I
authors.lastname: Santisteban
authors.forename: Lynette
authors.initials: L
authors.lastname: Fairbanks
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ragusa
authors.forename: Massimo
authors.initials: M
authors.lastname: Resti
authors.forename: Maurizio
authors.initials: M
authors.lastname: de Martino
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Chiara
authors.initials: C
authors.lastname: Azzari
mesh_terms: D000243:Adenosine Deaminase / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D000361:Agammaglobulinemia / Q000175:diagnosis*; D003839:Deoxyadenosines / Q000378:metabolism; D004789:Enzyme Activation; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D016130:Immunophenotyping; D007231:Infant, Newborn; D016131:Lymphocyte Subsets / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000097:blood* / Q000235:genetics; D012189:Retrospective Studies; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis*; D053719:Tandem Mass Spectrometry
chemical_list: D003839:Deoxyadenosines; D007136:Immunoglobulins; D011948:Receptors, Antigen, T-Cell; D000243:Adenosine Deaminase; C058118:2'-deoxyadenosine