Pediatr Neonatol. 2026 Aug 19:S1875-9572(26)00137-3. doi: 10.1016/j.pedneo.2026.05.006. Online ahead of print.
ABSTRACT
BACKGROUND: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is the most common inherited adrenal disorder in children. Clinical severity is determined by residual CYP21A2 enzyme activity. This study aimed to characterize the clinical and genetic spectrum of classic CAH and to evaluate genotype-phenotype correlations in a Taiwanese cohort.
METHODS: We retrospectively reviewed 53 patients with classic CAH (31 salt-wasting [SW], 22 simple virilizing [SV]) followed at Linkou Chang Gung Memorial Hospital between 1987 and 2023. Clinical characteristics, biochemical profiles, electrolyte disturbances, and CYP21A2 genotypes were analyzed. Virilization in females was graded using the Prader scale. Statistical analyses were performed using nonparametric methods.
RESULTS: Patients with SW CAH were diagnosed significantly earlier than those with SV CAH (median 16.4 days vs. 6.1 years, p < 0.0001) and exhibited more pronounced electrolyte abnormalities, including lower sodium (p = 0.0004) and higher potassium levels (p = 0.0061). Among 35 patients who underwent genetic testing (70 alleles), the most common variants were c.293-13A > G and p.Ile173Asn (c.518T > A), which were predominantly associated with SW and SV phenotypes, respectively. Female patients with SW CAH demonstrated more severe virilization (Prader stages 3-5 in 82.4%) compared with those with SV CAH (p = 0.0012). Overall genotype-phenotype concordance was high, although a minority of cases showed discordance between predicted enzymatic activity and clinical severity.
CONCLUSIONS: Salt-wasting CAH was the predominant form in this Taiwanese cohort, and the CYP21A2 mutation spectrum was consistent with global reports. The severity of virilization correlated with underlying enzymatic activity, supporting the clinical utility of genotyping for disease prediction and counseling. However, discordant cases highlight the potential role of modifying factors and underscore the need for individualized clinical management.
PMID:42680663 | DOI:10.1016/j.pedneo.2026.05.006
