Purpose: This study aimed to describe gene mutations and growth outcome in patients with 21-hydroxylase deficiency
Methods: Subjects were diagnosed as 21-hydroxylase deficiency by direct Sanger sequencing or multiple ligation-dependent probe amplification analysis and visited Pusan National University Children's Hospital from July 2008 to April 2019.We investigated the genotype, phenotype and growth profiles.
Results: Among 33 patients with congenital adrenal hyperplasia (CAH), 17 were females and 16 were males. Median age was 7.7years (1month-23.8yr).Twenty-seven (81.8%) had salt-wasting phenotype. Fourteen (42.4%) initially presented with 17 OHP elevation, with no other symptoms. Among 17 girls, thirteen (76.5%) had ambiguous genitalia and 7 (41.2%) received genitalia surgery. We evaluated 66 alleles from 33 patients. The distribution of 21-hydroxylase deficiency gene mutations revealed that intron 2 splice site (c.293-13A/C>G ) mutation was the most common (31.8%) followed by large/complete deletion (16.7%), and c.518T>A (15.2%), respectively. Three novel mutations (p.G111fs, p.Q319*, and homozygous complete deletion in CYP21A2 were detected. Ten (30.3%) needed growth hormone therapy due to short stature. Nine (47.4%) had bone age advanced more than 2 years. Five (15.2%) were treated for precocious puberty. Among 27 patients aged>2years, more than half (55.6%) were obese/overweight. When divided into two groups according to steroid dose(13.2mg/m2),more proportion of higher steroid dose group received growth hormone therapy than lower dose group(6.3% vs 52.9%, P=0.007).
Conclusion: Three novels and onerecurrent (c.293-13A/C>G) CYP21A2 mutations were identified .Careful monitoring of growth profile is needed for CAH patients, especially in those with high steroid dose.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology