Follow-up of 68 children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: relevance of genotype for management.
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.
Pinto
G
G
Pediatric Endocrinology Unit, Hôpital Necker-Enfants Malades, Assistance Publique-Hopitaux de Paris, 75743 Paris, France.
Tardy
V
V
Trivin
C
C
Thalassinos
C
C
Lortat-Jacob
S
S
Nihoul-Fékété
C
C
Morel
Y
Y
Brauner
R
R
D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000145:classification / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D001827:Body Height / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications; D016896:Treatment Outcome
D006854:Hydrocortisone