Abstract
OBJECTIVES: To explore the clinical and genetic characteristics of children with salt-wasting (SW) 21-hydroxylase deficiency (21-OHD) in Henan Province. METHODS: Clinical characteristics, laboratory results, and genetic findings were retrospectively reviewed for 165 children with SW 21-OHD who presented to the Department of Endocrinology and Genetic Metabolism, Children's Hospital Affiliated to Zhengzhou University, from August 2007 to November 2023. Associations between clinical characteristics and genotypes were analyzed. RESULTS: Of the 165 patients, 100 were biologically male and 65 female. The median age at diagnosis was 40 days in males and 28 days in females. Skin and mucosal hyperpigmentation occurred in 155 patients (93.9%), vomiting in 151 patients (91.5%), and failure to gain weight in 153 patients (92.7%). All females had clitoral hypertrophy. At presentation, 161 (97.6%) had adrenal crisis. Hyperkalemia (serum potassium >5.5 mmol/L) was present in 83.0% (137/165), and hyponatremia (serum sodium <135 mmol/L) in 93.9% (155/165). Elevated adrenocorticotropic hormone (ACTH) occurred in 96.4% (159/165), decreased cortisol in 90.3% (149/165), and elevated testosterone and 17-hydroxyprogesterone (17-OHP) in 100% (165/165). Six patients with male social gender had a 46,XX karyotype. All patients carried homozygous or compound heterozygous pathogenic variants in CYP21A2; 330 variants representing 29 types were identified, with c.293-13A/C>G (37.3%) and large deletions (22.4%) being most common. Twenty patients carried recombinant alleles between CYP21A2 and CYP21A1P. Across genotype groups, serum potassium, sodium, ACTH, testosterone, and cortisol showed no statistically significant differences (P>0.05), whereas 17-OHP levels differed significantly (P<0.05). CONCLUSIONS: SW 21-OHD typically presents with adrenal crisis. Hyperkalemia, hyponatremia, elevated 17-OHP, testosterone, and ACTH, together with decreased cortisol, support the diagnosis; definitive confirmation requires genetic testing. Genotype does not fully predict clinical phenotype.