Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: clinical, biochemical and molecular characteristics and long-term outcomes

Introduction

11β-hydroxylase (11β-OH) deficiency is the second most frequent cause of classic congenital adrenal hyperplasia (CAH) (5%–8% of cases). Clinically, it is characterized by virilization and arterial hypertension. The objective of this study was to describe the clinical, biochemical and genetic characteristics classic 11β-OH deficiency in patients managed in our hospital and its outcomes.

Patients and methods

Retrospective longitudinal, observational and descriptive study. Inclusion criteria: Patients with clinical features of virilization, high levels of 11-deoxycortisol and study of CYP11B1 gene with detection of pathogenic and likely pathogenic variants.

Results

We identified 6 patients (1 male, 5 female) from 4 families. In the 4 index cases, the median age at diagnosis was 2.3 years. The 46,XX patients exhibited a variable degree of virilization at diagnosis, with a predominance of Prader stage V, and one case of male sex assignment at birth. All patients had elevated serum concentrations of 17-hydroxyprogesterone and testosterone. Fifty percent of the patients had developed arterial hypertension during the follow-up, with onset at a median age of 9.3 years. Three 46,XX patients reached a median final height of 154 cm. Six different variants of theCYP11B1 gene were identified, 5 of which were novel variants (c.595 G > A, c.710 T > C, c.1156delG, c.395 + 2dupT, c.1159dupA).

Conclusions

There is considerable heterogeneity in the clinical presentation of patients with CAH due to 11β-OH deficiency. Early diagnosis and treatment are important to prevent complications and improve long-term outcomes. We report 6 different variants of the CYP11B1 gene, including 5 novel variants.