Genotype of Steroid 21-Hydroxylase Gene and Clinical Characteristics in Patients with Congenital Adrenal Hyperplasia 21-Hydroxylase Deficiency

Ko, Jung Min; Choi, Jin Ho; Kim, Gu Hwan; Yoo, Han Wook

Abstract

PURPOSE
This study was undertaken to characterize clinical features of congenital adrenal hyperplasia (CAH) with steroid 21-hydroxylase deficiency, identify appropriate dose of hydrocortisone to normalize endocrine abnormalities, and correlate between clinical phenotype and genotype of the patients.
METHODS
Endocrine and molecular evaluations were carried out in 42 patients at Asan Medical Center during the periods of December-1990 through July-2004. Endocrine laboratory study included the assay of plasma 17-hydroxyprogesterone (17-OHP), ACTH, androstenedione, testosterone, renin, and aldosterone by immunoradiometric assay (IRMA). Mutation study was performed by deletion analysis using specific polymerase chain reaction (PCR) for active gene (CYP21A2) with combination of pseudogene (CYP21A1P) primers as well as direct DNA sequencing of active gene. Auxological parameters, endocrine profiles and bone age by Greulich-Pyle method were monitored during treatment with hydrocortisone in 30 patients. Their medical records have been analyzed retrospectively. The patients were categorized as salt wasting type (SW) and simple virilization type (SV) depending on their clinical features. Auxological, endocrinological parameters, dose of hydrocortisone and genotype were statistically compared between these two group using SPSS 11.5 version.
RESULTS
Of the 30 patients, 24 patients were SW and 6 patients were SV. In the cases of SW, the boys were 0.17+/-0.08 years old and the girls were 0.08+/-0.08 years old at diagnosis. Initial ratio of bone age to chronologic age (BA/CA ratio) of the boys was 1.01+/-0.49 and of the girls was 2.25+/-2.67. In the cases of SV, the boys were 6.17+/-0.42 years old and the girls were 6.91+/-10.83 years old at diagnosis. Initial BA/CA ratio of the boys was 2.33+/-0.17 and of the girls was 1.64+/-0.80. Serum 17-OHP, ACTH and renin were normalized in all patients by hydrocortisone treatment. The dosage of hydrocortisone needed to normalize endocrinological features was 22.9+/-8.0 mg/m2/day in boys and 18.0+/-4.0 mg/m2/day in girls in the SW group, 12.5+/-3.8 mg/m2/day in boys and 18.4+/-0.7 mg/m2/day in girls in the SV group. Nineteen types of CYP21 mutation was observed in 42 patients. Q318X, R356W, c.293-13 A>G and null mutation were observed in the SW group.
CONCLUSION
The age at the diagnosis in SV was older than in SW. In SV, bone age was older than chronologic age at diagnosis. However, finally measured BA/CA ratio and the dosage of hydrocortisone were not different in two clinical types. There was genotype-phenotype correlation in CAH patients with 21-hydroxylase deficiency.