Clinical and molecular characteristics of simple virilizing congenital adrenal hyperplasia due to 21-hydroxylase deficiency: insight from a tertiary pediatric center in Vietnam
- Author:
Khanh Ngoc NGUYEN
1
;
Giang Thi Kim DANG
;
Ngoc Thi Bich CAN
;
Dien Minh TRAN
;
Thao Phuong BUI
;
Mai Nguyen Thi PHUONG
;
Huong Thu PHAM
;
Ngoc Diem NGO
;
Dung Chi VU
Author Information
- Publication Type:Original article
- From:Annals of Pediatric Endocrinology & Metabolism 2025;30(6):330-339
- CountryRepublic of Korea
- Language:English
-
Abstract:
Purpose:Simple virilizing congenital adrenal hyperplasia (SV-CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disease caused by pathogenic variants of the CYP21A2 gene. Children with SV-CAH often experience delayed diagnosis, presenting with pseudo-precocious puberty in males and genital virilization in females. Genotyping is essential for diagnosis, treatment, optimization, and phenotype prediction. This study describes the clinical and genetic characteristics of SV-CAH to guide treatment strategies.
Methods:From November 2016 to March 2023, 79 children (accounting for 34.3% of 230 CAH cases in the overall children’s cohort) from 75 families were classified as SV-CAH due to 21-OHD at the Vietnam National Children's Hospital. Forty-three children underwent CYP21A2 mutation analysis using multiplex ligation-dependent probe amplification and complete gene sequencing to detect pathogenic variants.
Results:Median age at diagnosis was 4.5 years (interquartile range, 1 day–22.3 years). There were 38.0% males and 62.0% females. The most common symptoms were penile enlargement in males (53.3%) and clitoromegaly (87.8%) in females; the height standard deviation (SD) at diagnosis was 1.90±1.79 SD (-2.02 to 5.43) according to the World Health Organization; and bone age advancement was 4.65±2.59 years. Genetic analysis identified 21 pathogenic variants and 22 genotypes in 43 children. The most common variant was p.I173N (47.7%); the most common genotype was p.I173N/p.I173N (16.3%).
Conclusion:Children with SV-CAH are often diagnosed late. To avoid that, early genetic analysis should be prioritized, especially for children diagnosed through newborn screening programs. Determining the genotype is crucial for optimizing treatment strategies, ensuring personalized management, and avoiding overtreatment.
