In this study, we describe the clinical presentation, steroid hormone production, and mutational spectrum of patients with 11βhydroxylase deficiency identified in Hungary. Data of eight patients (6 males, 2 females) with the classical form of 11β-hydroxylase deficiency were analyzed. Steroid hormones in blood were determined by RIA after chromatographic separation. Steroid hormone metabolites in urine were measured by GC-MS. The CYP11B1 gene was PCR amplified in 3 fragments and PCR products were directly sequenced. Patients presented with inappropriate virilization (pseudo precocious puberty in males and ambiguous genitalia in females). They had hypertension (130-160/85-100 mmHg) and hypokalemia (2.8-3.8 mmol/l), except two patients aged below 1.1 year. Serum levels of 11-deoxycorticosterone (DOC) were elevated (271-1700 ng/dl), 11-deoxycortisol concentrations were very high (8.5-49.4 μg/dl), and serum levels of 17-OHP were slightly increased (4-72 ng/ml), while those of corticosterone and cortisol were low normal or decreased. Urinary excretion of THS was elevated (5.6-42.3 mg/day), and was accompanied by low excretion of THE. Mutational analysis was performed in 7/8 patients. In two patients (siblings), a homozygous stop mutation (R141X) of the CYP11B1 gene was identified. One patient was homozygous for the R448H mutation, while another patient was homozygous for the T318R mutation. Two patients proved to be compound heterozygotes, one for T318R and R448C, and the other for delV161 and T318R. Sequence analysis of the CYP11B1 gene of one patient showed no alteration from the wild-type. In conclusion, patients with 11βhydroxylase deficiency can be identified among patients with inappropriate virilization by steroid profile measurements using highly specific methods. Mutations leading to incorrect amino acids in the critical regions of P450c11 result in a pathological decrease in 11β-hydroxylase enzyme activity, a high level of an active mineralocorticoid, DOC, and an increase in the secretion of adrenal androgens.
|Number of pages||8|
|Journal||Journal of Endocrine Genetics|
|Publication status||Published - Jan 1 2001|
- Congenital adrenal hyperplasia
- β-hydroxylase deficiency
ASJC Scopus subject areas