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Follow-up of 68 children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: relevance of genotype for management.

Pinto G., Tardy V., Trivin C., Thalassinos C., Lortat-Jacob S., Nihoul-Fekete C., Morel Y., Brauner R.

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.

J. Clin. Endocrinol. Metab. 88:2624-2633(2003) [PubMed] [Europe PMC]