Fan Lijun, Zhang Beibei, Li Lele, Gong Chunxiu
Department of Endocrinology, Genetics, Metabolism, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China.
Beijing Key Laboratory for Genetics of Birth Defects, Beijing Children's Hospital, National Center for Children's Health, Capital Medical University, Beijing, China.
Clin Endocrinol (Oxf). 2020 Dec;93(6):687-695. doi: 10.1111/cen.14277. Epub 2020 Jul 27.
Aromatase deficiency (AD) caused by cytochrome P450 family 19 subfamily A polypeptide 1 (CYP19A1) variants is characterized by a deficiency in androgen-to-oestrogen conversion.
To investigate the clinical characteristics and accurate management of aromatase-deficient children.
We described three 46, XX aromatase-deficient children, searched PubMed with "(aromatase deficiency) AND (46, XX OR ovaries)" and manually searched citations in identified studies for the literature review.
Two girls and one boy (3.4-9.2 years) with the 46, XX karyotype presented ambiguous genitalia and maternal antenatal virilization, normal-low height, delayed bone age, normal glucose and lipid profiles, markedly elevated follicle-stimulating hormone (FSH) levels and poor oestradiol responses to human menopausal gonadotropin stimulation. Ultrasound revealed normal-sized uterus and ovaries with undetectable follicles. Histopathology revealed primordial follicles and few primary follicles in ovaries. One patient presented granulosa and follicular membrane cell proliferation and interstitial sclerosis. We identified four CYP19A1 variants; c.146_158del and c.344G >A were unreported. We reviewed available data from thirty 46, XX patients (0.2-32 years). Some patients were not diagnosed until puberty/adulthood; three were initially misdiagnosed with congenital adrenocortical hyperplasia. The main characteristics were maternal antenatal virilization (21/29), ambiguous genitalia (mainly Prader IV or III, 19/23), delayed bone age (16/17), low bone mass (5/8), markedly elevated FSH levels and ovarian cysts (13/30).
46, XX AD is easily neglected or misdiagnosed. Ambiguous genitalia, maternal antenatal virilization and markedly elevated FSH levels are important diagnostic indicators. We described two novel variants, new histopathological features of ovaries and an early management strategy.
由细胞色素P450家族19亚家族A多肽1（CYP19A1）变体引起的芳香化酶缺乏症（AD）的特征是雄激素向雌激素转化不足。
探讨芳香化酶缺乏儿童的临床特征及精准管理。
我们描述了3例46,XX芳香化酶缺乏儿童，在PubMed上检索了“（芳香化酶缺乏症）AND（46,XX或卵巢）”，并手动检索了已识别研究中的参考文献进行文献综述。
2名女孩和1名男孩（3.4 - 9.2岁），核型为46,XX，表现为生殖器模糊和母亲产前男性化，身高正常偏低，骨龄延迟，血糖和血脂水平正常，促卵泡生成素（FSH）水平显著升高，对人绝经期促性腺激素刺激的雌二醇反应不佳。超声显示子宫和卵巢大小正常，未检测到卵泡。组织病理学显示卵巢中有原始卵泡和少量初级卵泡。1例患者出现颗粒细胞和卵泡膜细胞增殖以及间质硬化。我们鉴定出4种CYP19A1变体；c.146_158del和c.344G>A未被报道。我们回顾了30例46,XX患者（0.2 - 32岁）的现有数据。一些患者直到青春期/成年期才被诊断出来；3例最初被误诊为先天性肾上腺皮质增生。主要特征包括母亲产前男性化（21/29）、生殖器模糊（主要为普拉德IV或III级，19/23）、骨龄延迟（16/17）、低骨量（5/8）、FSH水平显著升高和卵巢囊肿（13/30）。
46,XX AD容易被忽视或误诊。生殖器模糊、母亲产前男性化和FSH水平显著升高是重要的诊断指标。我们描述了两种新变体、卵巢新的组织病理学特征和早期管理策略。
