Maternal, Child and Adolescent Health Center, State University of Health Sciences of Alagoas, Postgraduate Program in Health Sciences of the Institute of Biological and Health Sciences of the Federal University of Alagoas, Maceió, Brazil.
Medical Genetics Sector, Faculty of Medicine, Federal University of Alagoas, Maceió, Brazil.
Ital J Pediatr. 2022 Jun 10;48(1):89. doi: 10.1186/s13052-022-01284-9.
The Congenital Adrenal Hyperplasia due to 21 hydroxylase deficiency is the most common cause of genital ambiguity in persons with XX sexual chromosomes. Genital ambiguity among persons with XY sexual chromosomes comprises diverse and rare etiologies. The deficiency of 17-beta-hydroxysteroid dehydrogenase type 3 enzyme (HSD17B3) is a rare autosomal recessive disorder due to functionally altered variants of the HSD17B3 gene. In this disorder/difference of sex development, the conversion of androstenedione into testosterone is impaired. The appearance of external genitalia of 46,XY individuals varies from typically male to almost female.
We report on a child presenting severe ambiguous genitalia. Due to access constraints, specialized care did not start until the child was 10 months old. Parents are consanguineous and were born in an area of high isonymy that is a cluster for rare recessive diseases. A new homozygous missense variant c.785G > T was found in exon 10 of the HSD17B3 gene.
Researchers-clinicians and researchers-researchers collaborative efforts to elucidate the genetic basis of this disease were critical since this etiologic investigation is not available through the public health system. This case exemplifies the families' pilgrimage in cases of genital ambiguity due to a rare genetic condition. Recognizing the etiology was the baseline to provide information on prognosis and treatment options, and to shelter family and child doubts and hopes in order to better support their decisions.
21 羟化酶缺乏导致的先天性肾上腺皮质增生症是 XX 性染色体个体生殖器模糊的最常见原因。性染色体为 XY 的个体的生殖器模糊由多种罕见病因引起。17-β-羟类固醇脱氢酶 3 型（HSD17B3）缺乏是一种罕见的常染色体隐性遗传病，是由于 HSD17B3 基因突变导致该酶功能改变。在这种性别发育差异/障碍中，雄烯二酮向睾酮的转化受损。46,XY 个体的外生殖器外观从典型男性到几乎女性不等。
我们报告了一例表现为严重生殖器模糊的儿童病例。由于就诊受限，直到孩子 10 个月大时才开始接受专业治疗。患儿父母是近亲，出生在一个高同宗率地区，该地区是罕见隐性疾病的高发地。在 HSD17B3 基因的第 10 外显子中发现了一个新的纯合错义突变 c.785G>T。
研究人员-临床医生和研究人员-研究人员的合作努力对于阐明该疾病的遗传基础至关重要，因为这种病因调查无法通过公共卫生系统进行。这个病例说明了由于罕见的遗传条件导致生殖器模糊时，家庭的求医历程。明确病因是提供预后和治疗选择信息、解决家庭和孩子疑虑和希望的基础，以便更好地支持他们的决策。
