ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Pediatric Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1665306
Comprehensive characterization of 21-hydroxylase deficiency in a Chinese pediatric cohort: phenotype, steroid profiles and genetics
Provisionally accepted
- 1Second Hospital of Hebei Medical University, Shijiazhuang, China
- 2Kingmed Diagnostics (Beijing) co.Ltd, Beijing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Objective: This study aimed to investigate the clinical, steroid hormones and genetic characteristics of Chinese children with 21-hydroxylase deficiency (21OHD). Methods: This retrospective study included 115 children with 21OHD. Clinical data, steroid hormone levels, and genetic information were collected for overall and subgroup analyses. Clinical and steroid hormone characteristics were compared across clinical phenotypes and by sex. Within the salt-wasting (SW) group, characteristics were also compared between newborn screening (NBS)-diagnosed and clinically diagnosed patients. The relationship between Prader scores and both clinical phenotype and steroid hormone levels was analyzed, and the genotype-phenotype correlation, variation frequency and CAH-X CH-1 incidence were calculated. Results: The cohort comprised 76 (66.09%) SW, 27 (23.48%) simple virilizing (SV), and 12 (10.43%) non-classic (NC) patients. The overall levels of adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone(17OHP), and progesterone (P) levels were significantly elevated in SW and SV compared to NC patients. Girls with Prader scores ≥1 had higher hormone levels than those with normal external genitalia. Virilization was more severe in SW than SV girls. NBS significantly reduced the diagnostic delay for SW infants. Functional assays and SpliceAI prediction confirmed that a novel splice variant (c.203-1G>A) induces exon 2 skipping. We also report the first instance of cis double mutations (E3del8bp and p.V282L) on a single allele in two brothers. The allele frequency of p.V282L (5.16%) and CAH-X CH-1 incidence (11.32%) were higher than previously reported. Conclusion: This study expands the 21OHD mutational spectrum with two novel findings: a pathogenic splice-site variant (c.203-1G>A) and cis double mutations on a single allele. We demonstrate phenotype-specific differences in virilization and steroid hormones, underscoring the value of Prader scoring. NBS facilitated earlier diagnosis in SW patients, supporting its nationwide implementation in China. Our findings illustrate a distinct genetic architecture for 21OHD in the Chinese population, correlating with increased detection of NC cases.
Keywords: 21-hydroxylase deficiency, steroid hormones, Newborn screening, Genotype, CAH-X syndrome
Received: 14 Jul 2025; Accepted: 15 Sep 2025.
Copyright: © 2025 Chong, Xue, Pi, Zhang, Li, Xing, Chen and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Huifeng Zhang, 26400721@hebmu.edu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.