Endocrine Abstracts

Background and Objective: Congenital adrenal hyperplasia (CAH) is one of the most common diseases in pediatric endocrinology. Non-classical (NC-CAH) forms are characterized by milder enzyme dysfunction and manifests commonly in adolescence or adulthood. The most frequent form of NC-CAH occurs due to 21-hydroxylase deficiency which is caused by defects in the CYP21A2 gene. Our aim was to describe the most common 21-hydroxylase gene (CYP21A2) mutations in our geographical area in pediatric patients with clinical and biochemical diagnosis of NC-CAH and to determine bone age advance respect to Chronological age at diagnosis moment.

Setting and Method: A genetic study of the most frequent 21-hydroxylase mutations was requested in prepubertal patients with clinical and biochemical diagnosis of NC-CAH. Bone age at diagnosis was also determined using the Grewlich and Pyle reading methods. Main outcome measures 21-hydroxylase gene (CYP21A2) mutations.

Results: We evaluated 18 patients (12 women and 6 men) with a mean age at diagnosis (mean ± SD) of 7.61±2.23 years. The most frequent clinical presentation was precocious puberty (66.7%) followed by virilization (22.2%) and precocious puberty + apocrine sweating (5.6%); in 1 patient the genetic study was requested for a family history of NC-CAH without symptoms. In the genetic study, the most frequent genotypes were: V281L in heterozygosis (61.1%) and homozygosis (11.1%), I2splice in heterozygosis (5.6%), V281L/I2splice (5.6%), V281L/P453S (5.6%), P453S in heterozygosis (5.6%) and Cluster E6/V281L/L307 frameshift/Q318X (5.6%). Of the 36 alleles studied, the V281L mutation was found in 75%. Mean bone age advance was 1.83±0.71 years.

Conclusion: The NC-CAH is more frequent in the female sex, precocious puberty is the most common symptom and the V281L mutation is the most frequent in our environment. The patients affected usually present bone age advance respect to the chronological age at diagnosis.