Yami Channaiah Chethan, Memon Saba Samad, Sarathi Vijaya, Lila Anurag Ranjan, Barnabas Rohit, Raghav Darpan, Bhandare Vishwambhar V, Arya Sneha, Thakkar Hemangini, Patil Virendra Ashokrao, Karlekar Manjiri, Kunwar Ambarish, Bandgar Tushar
Department of Endocrinology, Seth GS Medical College and KEM Hospital, Parel, 400012 Mumbai, India.
Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Centre, 560066 Bengaluru, India.
Ann Endocrinol (Paris). 2024 Feb;85(1):48-55. doi: 10.1016/j.ando.2023.05.010. Epub 2023 Jun 20.
Aromatase deficiency is a rare disorder, with only a few cases reported in India. We describe a single-center experience in western India, with a systematic review of genetically proven 46,XX aromatase deficiency patients to evaluate hormonal parameters.
Retrospective review of case records, collating phenotypic and genotypic data and molecular modeling. Systematic review of 46,XX aromatase deficiency, analyzing data on gonadotropins, estrogen and androgens.
In the seven patients from our center, presentation was frequent in childhood or adolescence (4/7: delayed puberty or hyperandrogenism), with maternal virilization (4/7), predominance of Prader III/IV (5/7), and initial rearing as females (6/7). Three patients had hypoplastic ovaries. One patient had spontaneous regular menses. We report three novel (p.Arg115Pro, p.Arg192Pro, and c.145+1_145+4delins) and two recurrent variants (p.Val370Met, and c.145+1_145+4delins) in western and northern India, respectively. On systematic review (n=43), gonadotropins were elevated (FSH>LH) across ages (except preterm infants), androgens were elevated in about one-third of cases during childhood and puberty, and estradiol was lower than in controls in mini-puberty and puberty. Spontaneous thelarche and streak ovaries were significantly more frequent in patients with non-truncating and truncating variants, respectively.
We report uncommon presentations with possible founder variants, and highlight hormonal parameters across ages. Serum FSH levels were elevated except in preterms, and can be used as a diagnostic marker.
芳香化酶缺乏症是一种罕见疾病，在印度仅有少数病例报道。我们描述了印度西部一家单中心的经验，并对经基因证实的46,XX芳香化酶缺乏症患者进行系统回顾，以评估激素参数。
回顾病例记录，整理表型和基因型数据并进行分子建模。对46,XX芳香化酶缺乏症进行系统回顾，分析促性腺激素、雌激素和雄激素的数据。
在我们中心的7例患者中，发病常见于儿童期或青春期（4/7：青春期延迟或高雄激素血症），有母体男性化表现（4/7），Prader III/IV型占优势（5/7），最初均按女性抚养（6/7）。3例患者卵巢发育不全。1例患者有自发规律月经。我们分别在印度西部和北部报告了3种新变异（p.Arg115Pro、p.Arg192Pro和c.145+1_145+4delins）和2种重复变异（p.Val370Met和c.145+1_145+4delins）。在系统回顾（n = 43）中，各年龄段促性腺激素均升高（FSH>LH）（早产儿除外），约三分之一的病例在儿童期和青春期雄激素升高，在小青春期和青春期雌二醇低于对照组。非截短型和截短型变异患者中，自发乳房发育和条索状卵巢分别更为常见。
我们报告了伴有可能的奠基者变异的罕见表现，并强调了各年龄段的激素参数。除早产儿外，血清FSH水平升高，可作为诊断标志物。
