Pregnancy in a Chinese woman with nonclassical 11β-hydroxylase deficiency caused by novel compound heterozygous mutations: a case report, literature review and functional validation

Background Congenital adrenocortical hyperplasia caused by 11β-hydroxylase deficiency (11β-OHD) due to CYP11B1 mutations in 46,XX patients is typically characterized by hyporeninemic hypokalemia hypertension, virilization, precocious pseudopuberty, accelerated skeletal maturation and short stature. Impaired fertility has been reported in the virilizing 11β-OHD form unless properly treated. Case presentation: A 35-year-old female patient with nonclassical 11β-OHD due to novel compound heterozygous mutations (V316M; C262_F264del) in CYP11B1 suffered from menstrual irregularities, infertility, hirsutism and low-renin hypertension with typical hormone profiles including an elevated 11-deoxycorticosterone and testosterone. Her reduced fertility recovered after the initiation of corticosteroid therapy, and conception was later successfully achieved by in vitro fertilization and frozen-thawed embryo transfer. Functional characterization of CYP11B1 V316M and C262_F264del mutations in human adrenocortical cells confirmed 7%-16% of residual enzyme activity (V316M: 11.5% ± 2.4%; C262_F264del: 7.8% ± 2.9%; V316M; C262_F264del: 16.5% ± 0.6%). Conclusions We reported a successful pregnancy in a female patient with nonclassical 11β-OHD due to compound heterozygosity of novel CYP11B1 mutations by in vitro fertilization. The close coordination of care by a multidisciplinary medical team is beneficial for patients with congenital adrenocortical hyperplasia to achieve an accurate diagnosis, proper fertility management and uneventful pregnancy.