{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,17]],"date-time":"2025-01-17T05:23:05Z","timestamp":1737091385750,"version":"3.33.0"},"reference-count":12,"publisher":"Georg Thieme Verlag KG","issue":"01","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Aim Despite the high sensitivity of neonatal screening in detecting the\n                    classical form of congenital adrenal hyperplasia due to 21-hydroxylase\n                    deficiency, one of the unclear issues is identifying asymptomatic children with\n                    late onset forms. The aim of this nationwide study was to analyse the\n                    association between genotype and screened level of 17-hydroxyprogesterone in\n                    patients with the late onset form of 21-hydroxylase deficiency and to quantify\n                    false negativity.<\/jats:p><jats:p>\n          Methods In the Czech Republic, 1,866,129 neonates were screened\n                    (2006\u20132022). Among this cohort, 159 patients were confirmed to suffer from\n                    21-hydroxylase deficiency, employing the 17-hydroxyprogesterone\n                    birthweight\/gestational age-adjusted cut-off limits, and followed by the genetic\n                    confirmation. The screening prevalence was 1:11,737. Another 57 patients who\n                    were false negative in neonatal screening were added to this cohort based on\n                    later diagnosis by clinical suspicion. To our knowledge, such a huge nationwide\n                    cohort of false negative patients has not been documented before.<\/jats:p><jats:p>\n          Results Overall, 57 patients escaped from neonatal screening in the\n                    monitored period. All false negative patients had milder forms. Only one patient\n                    had simple virilising form and 56 patients had the late onset form. The\n                    probability of false negativity in the late onset form was 76.7%. The difference\n                    in 17-hydroxyprogesterone screening values was statistically significant\n                    (p&lt;0.001) between severe forms (median 478.8 nmol\/L) and milder (36.2 nmol\/L)\n                    forms. Interestingly, the higher proportion of females with milder forms was\n                    statistically significant compared with the general population.<\/jats:p><jats:p>\n          Conclusions A negative neonatal screening result does not exclude milder\n                    forms of 21-hydroxylase deficiency during the differential diagnostic procedure\n                    of children with precocious pseudopuberty.<\/jats:p>","DOI":"10.1055\/a-2433-0891","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T23:17:31Z","timestamp":1727911051000},"page":"20-24","source":"Crossref","is-referenced-by-count":0,"title":["21-Hydroxylase Deficiency Detected in Neonatal Screening: High\n                    Probability of False Negativity in Late Onset Form"],"prefix":"10.1055","volume":"133","author":[{"given":"Jan","family":"David","sequence":"additional","affiliation":[{"name":"Department of Children and Adolescents, Third Faculty of Medicine,\n                    Charles University and University Hospital Kralovske Vinohrady, Prague, Czech\n                    Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuzana","family":"Hrub\u00e1","sequence":"additional","affiliation":[{"name":"Department of Internal Hematology and Oncology, Centre of Molecular\n                    Biology and Genetics, Masaryk University and University Hospital Brno, Brno,\n                    Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hana","family":"Vinohradsk\u00e1","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Faculty of Medicine, Masaryk\n                    University and University Hospital Brno, Brno, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monika","family":"Hedelov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Children and Adolescents, Third Faculty of Medicine,\n                    Charles University and University Hospital Kralovske Vinohrady, Prague, Czech\n                    Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alena","family":"Fialov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, Third Faculty of\n                    Medicine, Charles University, Prague, Czech Republic"},{"name":"Department of Biostatistics, National Institute of Public Health,\n                    Prague, Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Votava","sequence":"additional","affiliation":[{"name":"Department of Children and Adolescents, Third Faculty of Medicine,\n                    Charles University and University Hospital Kralovske Vinohrady, Prague, Czech\n                    Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s00431-011-1656-6","article-title":"Lessons learned from 5 years of newborn screening for congenital adrenal\n                    hyperplasia in the Czech Republic: 17-hydroxyprogesterone, genotypes, and\n                    screening performance","volume":"171","author":"F Votava","year":"2012","journal-title":"Eur J Pediatr"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"71","DOI":"10.3390\/ijns6030071","article-title":"Update on the Swedish Newborn Screening for Congenital Adrenal Hyperplasia Due\n                    to 21-Hydroxylase Deficiency","volume":"6","author":"R H Zetterstr\u00f6m","year":"2020","journal-title":"Int J Neonatal Screen"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1515\/jpem-2018-0398","article-title":"High frequency of non-classical congenital adrenal hyperplasia form among\n                    children with persistently elevated levels of 17-hydroxyprogesterone after\n                    newborn screening","volume":"32","author":"P S Castro","year":"2019","journal-title":"J Pediatr Endocrinol Metab"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/cen.12543","article-title":"The spectrum of clinical, hormonal and molecular findings in 280 individuals\n                    with nonclassical congenital adrenal hyperplasia caused by mutations of the\n                    CYP21A2 gene","volume":"82","author":"S Livadas","year":"2015","journal-title":"Clin Endocrinol (Oxf)"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1210\/jc.2018-02468","article-title":"Combined gestational age-and birth weight-adjusted cutoffs for newborn screening\n                    of congenital adrenal hyperplasia","volume":"104","author":"N Pode-Shakked","year":"2019","journal-title":"J Clin Endocrinol Metab"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/humu.22981","article-title":"HGVS Recommendations for the Description of Sequence Variants: 2016 Update","volume":"37","author":"J T Dunnen","year":"2006","journal-title":"Hum Mutat"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1001\/jamapediatrics.2013.5321","article-title":"Nationwide neonatal screening for congenital adrenal hyperplasia in sweden: a\n                    26-year longitudinal prospective population-based study","volume":"168","author":"S Gidl\u00f6f","year":"2014","journal-title":"JAMA Pediatr"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1530\/eje.1.01929","article-title":"Estimation of the false-negative rate in newborn screening for congenital\n                    adrenal hyperplasia","volume":"152","author":"F Votava","year":"2005","journal-title":"Eur J Endocrinol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1111\/cge.13078","article-title":"A genetic epidemiology study of congenital adrenal hyperplasia in Italy","volume":"93","author":"A Gialluisi","year":"2018","journal-title":"Clin Genet"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.clinbiochem.2011.05.013","article-title":"Endocrine profile and phenotype-genotype correlation in unrelated patients with\n                    non-classical congenital adrenal hyperplasia","volume":"44","author":"N Skordis","year":"2011","journal-title":"Clin Biochem"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3390\/ijns6030063","article-title":"Evaluation of a Two-Tier Screening Pathway for Congenital Adrenal Hyperplasia in\n                    the New South Wales Newborn Screening Programme","volume":"6","author":"F Lai","year":"2020","journal-title":"Int J Neonatal Screen"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e4487","DOI":"10.1210\/clinem\/dgab464","article-title":"Second-tier Testing for 21-Hydroxylase Deficiency in the Netherlands: A Newborn\n                    Screening Pilot Study","volume":"106","author":"K Stroek","year":"2021","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2433-0891.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T23:36:17Z","timestamp":1737070577000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2433-0891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,2]]},"references-count":12,"journal-issue":{"issue":"01","published-online":{"date-parts":[[2025,1,16]]},"published-print":{"date-parts":[[2025,1]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2433-0891","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"type":"print","value":"0947-7349"},{"type":"electronic","value":"1439-3646"}],"subject":[],"published-other":{"date-parts":[[2024,10,2]]},"published":{"date-parts":[[2024,10,2]]}}}