Servicio de Endocrinología, Hospital de Pediatría Garrahan, Buenos Aires, Argentina.
Hospital Regional de Concepción, Tucumán, Argentina.
Horm Res Paediatr. 2018;90(4):275-282. doi: 10.1159/000492128. Epub 2018 Aug 31.
Aromatase deficiency is a rare autosomal recessive disorder. 46,XY-affected patients often remain undiagnosed until late puberty. Only 2 pediatric cases have been reported. Data on pubertal development in affected males are scarce.
To report the clinical phenotype and hormonal studies of an aromatase-deficient boy during the prepubertal and early pubertal period.
The patient was the older brother of a 46,XX girl with aromatase deficiency. Molecular analysis revealed a previously reported homozygous mutation (Arg192Cys) in the CYP19A1 gene. Pubertal onset was at 9.8 years. At 11.3 years of age, signs of rapidly progressive puberty were seen. Laboratory tests revealed normal pubertal basal and GnRH-stimulated gonadotropin levels, normal Sertoli cell markers, and increased testosterone. The prepubertal lumbar spine bone mineral density (BMD) was normal but pubertal bone mineral accrual was incomplete, leading to osteopenia.
Estrogen restraint on gonadotropin secretion has been demonstrated in animal and human models. Interestingly, our patient presented with accelerated puberty and apparently normal pituitary gonadal function. These findings suggest that aromatase activity may be required to define pubertal progression in boys. Estrogen deficiency due to aromatase deficiency is responsible for insufficient bone mineral accrual during puberty.
芳香酶缺陷是一种罕见的常染色体隐性遗传疾病。46,XY 受影响的患者通常直到青春期后期才被诊断出来。仅报道过 2 例儿科病例。有关受影响男性青春期发育的数据很少。
报告一名芳香酶缺陷男孩在青春期前和早期青春期的临床表型和激素研究。
该患者是一名芳香酶缺陷 46,XX 女孩的哥哥。分子分析显示 CYP19A1 基因中存在先前报道的纯合突变（Arg192Cys）。青春期开始于 9.8 岁。11.3 岁时，出现快速进展性青春期的迹象。实验室检查显示正常的青春期基础和 GnRH 刺激的促性腺激素水平、正常的支持细胞标志物和增加的睾酮。青春期前的腰椎骨密度（BMD）正常，但青春期骨矿物质积累不完全，导致骨质疏松症。
在动物和人类模型中已经证明了雌激素对促性腺激素分泌的抑制作用。有趣的是，我们的患者表现出加速的青春期和明显正常的垂体性腺功能。这些发现表明，芳香酶活性可能是定义男孩青春期进展所必需的。由于芳香酶缺陷导致的雌激素缺乏是青春期骨矿物质积累不足的原因。
