The Spectrum From Classic to Non-Classic 11β-Hydroxylase Deficiency

Abstract

Background: Given the rarity of 11β-hydroxylase deficiency (11βOHD), there is a paucity of the data about the differences in clinical and biochemical characteristics of classic (C-11βOHD) and non-classic 11βOHD (NC-11βOHD).Objective: To characterize a multicenter pediatric cohort with 11βOHD. Method: The clinical and biochemical characteristics were retrieved. CYP11B1 gene sequencing was performed. Seventeen plasma steroids were quantified by liquid chromatography-mass spectrometry and compared to that of controls. Results: 102 patients (C-11βOHD; n=92, NC-11βOHD; n=10) from 76 families (46,XX; n=53) had biallelic CYP11B1 mutations (novel 9 out of 30). Five 46,XX patients (10%) were raised as males. Nineteen patients (19%) had initially been misdiagnosed with 21-hydroxylase deficiency. Female final height was 152 cm (-1.85SDS) and male 160.4 cm (-2.56SDS). None of the NC-11βOHD girls had ambiguous genitalia (C-11βOHD 100%) and none of the NC-11βOHD patients were hypertensive (C-11βOHD 50%). Compared to NC-11βOHD, C-11βOHD patients were diagnosed earlier (1.33 vs. 6.9 years, p 2.2, <1.5 and <0.1 had 100% specificity to segregate C-11βOHD, NC-11βOHD and control groups. Conclusion: NC-11βOHD can escape from clinical attention due to relatively mild clinical presentation. However, steroid profiles enable the diagnosis, differential diagnosis, and subtyping of 11βOHD. Funding Statement: This work has been supported by the Medical Research Council of Marmara University (Project Grant SAG-A-120418-0152, TG). Declaration of Interests: The authors have nothing to disclose. Ethics Approval Statement: The study was performed with the approval of the Ethics Committee of Marmara University Faculty of Medicine, Istanbul, Turkey (09.2017.476). Patients and/or parents provided written informed consent.