A provisionary screening programme for 21-hydroxylase deficiency (21-OHD) was initiated in Beijing in 2014. The aim of this study was to investigate the incidence and the associated clinical characteristics of neonatal congenital adrenal hyperplasia (CAH) in Beijing and to provide evidence-based guidance for its application in CAH screening.
Live birth newborns (n=44,360) were screened for CAH in Beijing from July 2014 to April 2018. The levels of 17-hydroxyprogesterone (17-OHP) in the blood were estimated using the time-resolved fluoroimmunoassay. Neonates with a positive result and a level >30 nmol/L of 17-OHP were called for a retest. CAH was diagnosed based on further laboratory findings combined with clinical signs, such as weight loss, feeding difficulties, skin pigmentation, and atypical genitalia. Through a review of medical records, the clinical findings including molecular data were reported.
Of the 44,360 neonates screened, 280 cases were deemed positive. Of these, 203 neonates were recalled for further tests and six patients (three boys and three girls) were diagnosed with CAH. Five cases of classic salt-wasting and one case of simple virilising 21-OHD were identified. The incidence of CAH in Beijing was 1:7393. The most frequent 21-OHD mutation was c.293-13C/A>G.
The incidence of CAH in Beijing was higher than the national average. The results support the need for neonatal CAH screening in Beijing. This pilot study demonstrates the clinical characteristics of 21-OHD through newborn screening. Early detection and treatment through neonatal screening may reduce mortality rates and optimise developmental outcomes.
The authors express their gratitude to MyGenostics incorporation in Beijing for assistance with the genetic sequencing.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
1. Concolino P, Mello E, Zuppi C, Capoluongo E. Molecular diagnosis of congenital adrenal hyperplasia due to 21-hydroxylase deficiency: an update of new CYP21A2 mutations. Clin Chem Lab Med 2010;48:1057–62.10.1515/CCLM.2010.239Search in Google Scholar PubMed
2. Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, et al. Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2010;95:4133–60.10.1210/jc.2009-2631Search in Google Scholar PubMed PubMed Central
3. Subspecialty Group of Newborn Screening, Society of Birth Defects Prevention and Control, Chinese Preventive Medicine Association, Subspecialty Group of Clinical Genetics, Society of Adolescent Medicine, Chinese Medical Doctor Association, Chinese Society of Pediatric Endocrinology and Metabolism. Consensus statement on neonatal screening for congenital adrenal hyperplasia. Zhonghua Er Ke Za Zhi 2016;54:404–9.Search in Google Scholar
4. Gidlöf S, Wedell A, Guthenberg C, von Döbeln U, Nordenström A. Nationwide neonatal screening for congenital adrenal hyperplasia in Sweden: a 26-year longitudinal prospective population-based study. JAMA Pediatr 2014;168:567–74.10.1001/jamapediatrics.2013.5321Search in Google Scholar PubMed
6. White PC, Speiser PW. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr Rev 2000;21:245–91.Search in Google Scholar
7. Pearce M, DeMartino L, McMahon R, Hamel R, Maloney B, et al. Newborn screening for congenital adrenal hyperplasia in New York State. Mol Genet Metab Rep 2016;7:1–7.10.1016/j.ymgmr.2016.02.005Search in Google Scholar PubMed PubMed Central
8. Liang Y, Luo XP. The research advances of Children’s endocrine system diseases. Chin J Prac Pediatr 2013;28:324–7.Search in Google Scholar
9. Tian LP, Bu XP. Neonatal screening for congenital adrenal hyperplasia in Jinan areas. Matern Child Health Care Chin 2012;27:1666–8.Search in Google Scholar
11. Du ML. 21-hydroxylase deficiency. In: Gu XF, editor. Clinical genetic metabolic disease. Beijing: People’s Health Publishing House, 2015;296–303.Search in Google Scholar
12. Mass Screening Committee, Japanese Society for Pediatric Endocrinology, Japanese Society for Mass Screening. Guidelines for diagnosis and treatment of 21-hydroxylase deficiency (2014 revision). Clin Pediatr Endocrinol 2015;24:77–105.10.1297/cpe.24.77Search in Google Scholar PubMed PubMed Central
13. de Carvalho DF, Miranda MC, Gomes LG, Madureira G,Marcondes JA, et al. Molecular CYP21A2 diagnosis in 480 Brazilian patients with congenital adrenal hyperplasia before newborn screening introduction. Eur J Endocrinol 2016;175:107–16.10.1530/EJE-16-0171Search in Google Scholar PubMed
14. Anandi VS, Shaila B. Evaluation of factors associated with elevated newborn 17-hydroxyprogesterone levels. J Pediatr Endocrinol Metab 2017;30:677–81.10.1515/jpem-2016-0459Search in Google Scholar PubMed
15. Su YQ, Zhu WB, Wang J, Zhou JF, Zhao H, et al. Neonatal 17-hydroxyprogesterone normal levels and its influencing factors. Chin J Perinat Med 2015;18:687–91.Search in Google Scholar
16. Hayashi GY, Carvalho DF, De Miranda MC, Faure C, Vallejos C, et al. Neonatal 17-hydroxyprogesterone levels adjusted according to age at sample collection and birth-weight improve the efficacy of congenital adrenal hyperplasia newborn screening. Clin Endocrinol (Oxf) 2017;86:480–7.10.1111/cen.13292Search in Google Scholar PubMed
17. Luo C, Fan X, Li W, Geng GX, Lin CJ, et al. Comparison analysis of two cut-off establishing methods for newborn congenital adrenal hyperplasia screening. Chin J Evid Based Pediats 2016;11:21–5.Search in Google Scholar
18. Wang RF, Gu XF, Ye J, Han LS, Qiu WJ, et al. Analysis of phenotypes and genotypes in 66 patients with 21-hydroxylase deficiency identified by neonatal screening. Zhonghua Er Ke Za Zhi 2016;54:679–85.Search in Google Scholar
19. Tarini BA. The value of time in assessing the effectiveness of newborn screening for congenital adrenal hyperplasia. JAMA Pediatr 2014;168:515–6.10.1001/jamapediatrics.2014.246Search in Google Scholar PubMed
20. Bonfig W. Growth and development in children with classic congenital adrenal hyperplasia. Curr Opin Endocrinol Diabetes Obes 2017;24:39–42.10.1097/MED.0000000000000308Search in Google Scholar PubMed
©2019 Walter de Gruyter GmbH, Berlin/Boston