title: Neonatal screening: identification of children with 11β-hydroxylase deficiency by second-tier testing.
abstract: BACKGROUND
  21-Hydroxylase deficiency (21-OHD) is the target disease of newborn screening for congenital adrenal hyperplasia (CAH). We describe the additional detection of patients suffering from 11β-hydroxylase deficiency (11-OHD) by second-tier testing.
  
  
  METHODS
  Over a period of 5 years, screening for CAH was done in a total of 986,098 newborns by time-resolved immunoassay (DELFIA®) for 17α-hydroxyprogesterone (17-OHP). Positive samples were subsequently analyzed in an LC-MS/MS second-tier test including 17-OHP, cortisol, 11-deoxycortisol, 4-androstenedione and 21-deoxycortisol.
  
  
  RESULTS
  In addition to 78 cases of 21-OHD, 5 patients with 11-OHD were identified. Diagnostic parameters were a markedly elevated concentration of 11-deoxycortisol in the presence of a low level of cortisol. Androstenedione was also increased. In contrast to 21-OHD, concentrations of 21-deoxycortisol were normal.
  
  
  CONCLUSIONS
  Steroid profiling in newborn blood samples showing positive results in immunoassays for 17-OHP allows for differentiating 21-OHD from 11-OHD. This procedure may not detect all cases of 11-OHD in the newborn population because there may be samples of affected newborns with negative results for 17-OHP in the immunoassay.
authors.affiliation: Department of Neuropediatrics, Children's Hospital, Ruhr University of Bochum, Bochum, Germany. n.janzen@klinikum-bochum.de
authors.forename: Nils
authors.initials: N
authors.lastname: Janzen
authors.forename: Felix G
authors.initials: FG
authors.lastname: Riepe
authors.forename: Michael
authors.initials: M
authors.lastname: Peter
authors.forename: Stefanie
authors.initials: S
authors.lastname: Sander
authors.forename: Ulrike
authors.initials: U
authors.lastname: Steuerwald
authors.forename: Eckhard
authors.initials: E
authors.lastname: Korsch
authors.forename: Friedrich
authors.initials: F
authors.lastname: Krull
authors.forename: Hermann L
authors.initials: HL
authors.lastname: Müller
authors.forename: Sabine
authors.initials: S
authors.lastname: Heger
authors.forename: Christoph
authors.initials: C
authors.lastname: Brack
authors.forename: Johannes
authors.initials: J
authors.lastname: Sander
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000097:blood; D000312:Adrenal Hyperplasia, Congenital / Q000097:blood* / Q000175:diagnosis*; D000735:Androstenedione / Q000097:blood; D003350:Cortodoxone / Q000097:blood; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D015997:Neonatal Screening / Q000379:methods; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics
chemical_list: D000735:Androstenedione; C003556:21-deoxycortisol; D019326:17-alpha-Hydroxyprogesterone; D013252:Steroid 11-beta-Hydroxylase; D003350:Cortodoxone; D006854:Hydrocortisone