European Journal of Pediatrics

, Volume 166, Issue 1, pp 1–4 | Cite as

Prevalence of congenital adrenal hyperplasia among sudden infant death in the Czech Republic and Austria

  • Kristina A. Strnadová
  • Felix Votava
  • Jan Lebl
  • Adolf Mühl
  • Chike Item
  • Olaf A. Bodamer
  • Toni Torresani
  • Ivan Bouška
  • Franz Waldhauser
  • Wolfgang Sperl
Original Paper

Abstract

This study aimed to estimate the number of infants who died of unrecognized congenital adrenal hyperplasia (CAH) in Austria and the Czech Republic within the past 13 years, before the introduction of adequate neonatal screening. The study was based on retrospective analysis of neonatal screening cards of 242 infants who died suddenly between 7 days and 12 months of age and whose cause of death could not be identified. 17-hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay and positive samples were subsequently genotyped. Three infants out of 242 may have had unrecognized CAH due to CYP21 (steroid 21-hydroxylase) gene defect. Their newborn 17-OHP levels and CYP21 genotypes were 706 nmol/l and del/conv//del/conv, 53 nmol/l and I2//I2, and 811 nmol/l and I2//Gln318stop, respectively. CAH due to CYP21 defect can lead to sudden unexpected death without prior symptoms typical for the condition. Hence, newborn screening would have prevented these deaths had it been available. In addition, we have shown that the I2 point mutation that is expected to lead to simple virilizing form may lead to a fatal outcome.

Keywords

Sudden infant death syndrome Neonatal screening Congenital adrenal hyperplasia 

Abbreviations

17-OHP

17-hydroxyprogesterone

CAH

Congenital adrenal hyperplasia

CYP21

Gene encoding steroid 21-hydroxylase

Del/conv//del/conv

chimericCYP21/CYP21//chimericCYP21/CYP21

I2//I2

656A/C > G//656A/C > G

I2//Gln318stop

656A/C > G//Gln318stop

SIDS

Sudden infant death syndrome

References

  1. 1.
    Fitness J, Dixit N, Webster D, Torresani T, Pergolizzi R, Speiser PW, Day DJ (1999) Genotyping of CYP21, linked chromosome 6p markers, and a sex-specific gene in neonatal screening for congenital adrenal hyperplasia. J Clin Endocrinol Metab 84:960–966PubMedCrossRefGoogle Scholar
  2. 2.
    Gruneiro-Papendieck L, Prieto L, Chiesa A, Bengolea S, Bossi G, Bergadá C (2001) Neonatal screening program for congenital adrenal hyperplasia: adjustments to the recall protocol. Horm Res 55:271–277PubMedCrossRefGoogle Scholar
  3. 3.
    Honour JW, Torresani T (2001) Evaluation of neonatal screening for congenital adrenal hyperplasia. Horm Res 55:206–211PubMedCrossRefGoogle Scholar
  4. 4.
    Hughes I (2002) Congenital adrenal hyperplasia: phenotype and genotype. J Pediatr Endocrinol Metab 15:1329–1340PubMedGoogle Scholar
  5. 5.
    Kovács J, Votava F, Heinze G, Sólyom J, Lebl J, Pribilincová Z, Frisch H, Battelino T, Waldhauser F (2001) Lessons from 30 years of clinical diagnosis and treatment of congenital adrenal hyperplasia in five middle European countries. J Clin Endocrinol Metab 86:2958–2964PubMedCrossRefGoogle Scholar
  6. 6.
    Krous HF, Beckwith JB, Byard RW, Rognum TO, Bajanowski T, Corey T, Cutz E, Hanlick R, Keens TG, Mitchell EA (2004) Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach. Pediatrics 114:234–238PubMedCrossRefGoogle Scholar
  7. 7.
    Olgemöller B, Roscher AA, Liebl B, Fingerhut R (2003) Screening for congenital adrenal hyperplasia: adjustment of 17-hydroxyprogesterone cut-off values to both age and birth weight markedly improves the predictive value. J Clin Endocrinol Metab 88:5790–5794PubMedCrossRefGoogle Scholar
  8. 8.
    Pang S, Wallace MA, Hofman L, Thuline HC, Dorche C, Lyon ICT, Dobbins RH, Kling S, Fujieda K, Suwa S (1988) Worldwide experience in newborn screening for classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Pediatrics 81:866–874PubMedGoogle Scholar
  9. 9.
    Ruppen W, Hagenbuch N, Jöhr M, Christen P (2003) Cardiac arrest in an infant with congenital adrenal hyperplasia. Acta Anaesthesiol Scand 47:104–105PubMedCrossRefGoogle Scholar
  10. 10.
    Therrell BL, Berenbaum SA, Manter-Kapanke V, Simmank J, Korman K, Prentice L, Gonzalez J, Gunn S (1998) Results of screening 1.9 million Texas newborns for 21-hydroxylase deficient congenital adrenal hyperplasia. Pediatrics 101:583–590PubMedCrossRefGoogle Scholar
  11. 11.
    Torres N, Mello MP, Germano CMR, Elias LLK, Moreira AC, Castro M (2003) Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia. Braz J Med Biol Res 36:1311–1318PubMedGoogle Scholar
  12. 12.
    Török D, Mühl A, Votava F, Heinze G, Sólyom J, Crone J, Stöckler-Ipsiroglu S, Waldhauser F (2002) Stability of 17-hydroxyprogesterone in dried blood spots after autoclaving and prolonged storage. Clin Chem 48:370–372PubMedGoogle Scholar
  13. 13.
    White PC, Speiser PW (2000) Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 21:245–291PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Kristina A. Strnadová
    • 1
    • 2
  • Felix Votava
    • 1
  • Jan Lebl
    • 1
  • Adolf Mühl
    • 2
  • Chike Item
    • 2
  • Olaf A. Bodamer
    • 2
  • Toni Torresani
    • 3
  • Ivan Bouška
    • 4
  • Franz Waldhauser
    • 2
  • Wolfgang Sperl
    • 5
  1. 1.Department of Pediatrics, 3rd Faculty of MedicineCharles UniversityPragueCzech Republic
  2. 2.Division of Biochemical and Paediatric Genetics, Department of General PaediatricsMedical University of ViennaViennaAustria
  3. 3.Department of EndocrinologyUniversity Children’s HospitalZurichSwitzerland
  4. 4.Department of Forensic Medicine, 2nd Faculty of MedicineCharles UniversityPragueCzech Republic
  5. 5.Department of General PediatricsParacelsus Medical School, LandeskrankenhausSalzburgAustria

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