Genetic characteristics and clinical features of pediatric congenital adrenal hyperplasia in Korea.

PURPOSE: Despite the clinical importance of congenital adrenal hyperplasia (CAH), comprehensive data on subtype distribution, genetic characteristics, and the impact of newborn screening in Korea are limited. METHODS: We analyzed the genetic profiles and clinical characteristics at diagnosis in 368 patients with CAH diagnosed before 19 years of age from the Multicenter Networks for Ideal Outcomes of Pediatric Rare Endocrine and Metabolic Diseases in Korea (OUTSPREAD) cohort. RESULTS: 21-hydroxylase deficiency (21-OHD) was the most prevalent CAH subtype (299 cases, 85.7%; 208 genetically confirmed and 91 clinically diagnosed), followed by lipoid congenital adrenal hyperplasia (LCAH; 9.5%) and 17α-hydroxylase deficiency (17α-OHD; 3.7%), accounting for 98.8% of cases. Frequent variants included c.293-13 C > G and p.Ile173Asn in 21-OHD, whereas p.Gln258Ter and p.His373Leu predominated in LCAH and 17α-OHD, consistent with East Asian population databases. Genotype-phenotype correlation analysis in 21-OHD demonstrated high positive predictive value, with genotypes characterized by minimal or absent residual enzyme activity associated with classic CAH in over 95% of cases. Among patients with salt-wasting 21-OHD, diagnosis occurred significantly earlier after newborn screening introduction, regardless of karyotype (46,XX: median 18.3 vs. 9.1 days, P = 0.031; 46,XY: 29.1 vs. 18.3 days, P = 0.019), along with a significant reduction in salt-wasting-related symptoms at diagnosis (46,XX: 33.3% vs. 10.5%, P = 0.031; 46,XY: 87.5% vs. 21.6%, P < 0.001). CONCLUSION: This national multicenter cohort study provides comprehensive genetic and clinical characterization of pediatric CAH in Korea, particularly in delineating CAH subtype distribution and the impact of newborn screening.