Congenital adrenal hyperplasia (CAH), predominantly caused by 21-hydroxylase deficiency (21-OHD), arises from mutations in CYP21A2. This frequently occurs via gene conversion events between CYP21A2 and its pseudogene, leading to impaired 21-hydroxylase activity and subsequent CAH manifestations.

We encountered a case of classic CAH, characterized by electrolyte imbalances (hyponatremia: 125.10 mmol/L; hyperkalemia: 7.06 mmol/L), hyperpigmentation, and markedly elevated endocrine marker levels (17-hydroxyprogesterone: 319.91 nmol/L; adrenocorticotropic hormone: 611.00 pg/mL) in a male neonate. Through genetic diagnostics, we identified a maternal-derived deletion of CYP21A2 exons 1–7 combined with paternal-originated compound heterozygous mutations (c.293-13A/C>G in intron 2 and c.332_339 deletion in exon 3). Implementation of early genetic diagnosis revealed 21-OHD, and immediate therapeutic intervention was initiated within 11 days after the birth of the patient. Long-term treatment, including oral hydrocortisone, fludrocortisone, and 0.9% sodium chloride, provided effective clinical control and management, as determined by longitudinal follow-up monitoring of serum electrolyte profiles, endocrine function, and physical development.

This case provided critical insights into the genotype–phenotype correlations of classic 21-OHD. Our findings will contribute to precision medicine for managing this rare endocrine disorder during critical infancy periods, and emphasize the need for comprehensive genetic diagnostics and educational values for neonatal 21-OHD care.

The datasets for this article are not publicly available due to concerns regarding participant/patient anonymity. Requests to access the datasets should be directed to the corresponding author.

The studies involving humans were approved by the ethics committee of Chengdu Women's and Children's Central Hospital, Chengdu, China (No. 2023-73). The studies were conducted in accordance with the local legislation and institutional requirements.

Written informed consent for participation in this study was provided by the participants' legal guardians/next of kin. Written informed consent was obtained from the minor(s)' legal guardian/next of kin for the publication of any potentially identifiable images or data included in this article.

Y.Y.: Conceptualization, data curation, methodology, validation, writing—original draft, writing—review and editing. X.H.: Investigation, methodology, software, and validation. Y.S.: Investigation, methodology, validation, and resources. C.H.: Methodology and validation. J.Y.: Methodology and validation. Q.L.: Writing—review and editing, investigation, methodology, resources, supervision, and validation.

Received: 28 March 2025

Accepted: 26 June 2025

Accepted Manuscript online:
03 July 2025

Article published online:
18 July 2025

© 2025. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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