Follow-Up of 68 Children with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Relevance of Genotype for Management

• Published in: The journal of clinical endocrinology and metabolism 2003-06, Vol.88 (6), p.2624-2633
• Main Authors: Pinto, G., Tardy, V., Trivin, C., Thalassinos, C., Lortat-Jacob, S., Nihoul-Fékété, C., Morel, Y., Brauner, R.
• Format: Article
• Language: English
• Subjects: Adolescent; Adrenal Hyperplasia, Congenital - classification; Adrenal Hyperplasia, Congenital - drug therapy; Adrenal Hyperplasia, Congenital - genetics; Adrenal Hyperplasia, Congenital - pathology; Body Height - drug effects; Child; Child, Preschool; Female; Humans; Hydrocortisone - adverse effects; Hydrocortisone - therapeutic use; Infant; Infant, Newborn; Male; Metabolism, Inborn Errors - complications; Treatment Outcome
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2002-021433

The phenotype of congenital adrenal hyperplasia (CAH) varies greatly. The purpose of this study was to optimize diagnosis and follow-up by comparing phenotype with genotype. Sixty-eight patients with CAH due to 21-hydroxylase deficiency were studied by clinical, hormonal, and molecular genetic methods. Patients were classified according to predicted mutation severity: group 0, null mutation (17.6%); group A, homozygous for IVS2 splice mutation or compound heterozygous for IVS2 and null mutations (33.8%); group B, homozygous or compound heterozygous for I172N mutation (14.7%); group C, homozygous or compound heterozygous for V281L or P30L mutations (26.5%); and group D, mutations with unknown enzyme activity (7.4%). All group 0 and A patients had the salt-wasting form, and group C had nonclassical forms. Group B included five salt-wasting and five simple virilizing forms. Groups 0 and A were younger at diagnosis (P < 0.02), and females were more virilized than those in group B. Group B had higher basal plasma 17-hydroxyprogesterone (564 ± 162 nmol/liter) and testosterone (11 ± 3 nmol/liter) levels than group C [59 ± 13 nmol/liter (P < 0.001) and 1.4 ± 0.2 nmol/liter (P < 0.005), respectively]. Hydrocortisone doses given to groups 0, A, and B were similar at all ages, but lower in group C (P < 0.01). Final height was below target height in classical (n = 16; −2 ± 0.2 sd score; P < 0.02) and nonclassical (n = 11; −1.2 ± 0.4 sd score; P < 0.03) forms. The severity of the genetic defects and the clinical-laboratory features are well correlated. Genotyping, combined with neonatal screening and optimal medical and surgical treatment, can help in the management of CAH.