Bonnet Estelle, Winter Mathias, Mallet Delphine, Plotton Ingrid, Bouvattier Claire, Cartigny Maryse, Martinerie Laetiti, Polak Michel, Bachelot Anne, Huet Frédéric, Baron Sabine, Houang Muriel, Soskin Sylvie, Lienhardt Anne, Bertherat Jérôme, Amouroux Cyril, Bouty Aurore, Duranteau Lise, Besson Rémi, El Ghoneimi Alaa, Samara-Boustani Dinane, Becmeur François, Kalfa Nicolas, Paris Françoise, Medjkane François, Brac de la Perrière Aude, Bretones Patricia, Lejeune Hervé, Nicolino Marc, Mouriquand Pierre, Gorduza Daniela-Brindusa, Gay Claire-Lise
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service d'endocrinologie pédiatrique, Bron, France.
Centre National de Référence Maladies Rares du développement génital du fœtus à l'adulte DEV-GEN, Hospices Civils de Lyon, Bron, France.
Endocr Connect. 2023 Feb 14;12(3). doi: 10.1530/EC-22-0227. Print 2023 Mar 1.
To examine the changes in diagnostic practices and clinical management of patients with 5α-reductase type 2 (SRD5A2) or 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) deficiency since molecular diagnoses became available.
Clinical, laboratory, and therapeutic data were retrieved from the medical records of 52 patients with a molecular diagnosis of SRD5A2 (n = 31) or HSD17B3 (n = 21) deficiency. Temporal trends regarding age at assessment and initial sex assignment over 1994-2020 were qualitatively analyzed. Age at molecular diagnosis was compared between two subgroups of patients according to their year of birth.
Fifty-eight percent (n = 30) patients were diagnosed during the perinatal period, 33% (n = 17) during infancy, and 9% (n = 5) during adolescence or adulthood. Over the studied period, the patients' age at initial assessment and diagnosis frankly decreased. The median (range) age at diagnostic confirmation was 10.5 (0-53.2) years for patients born before 2007 and 0.4 (0-9.3) years for those born in 2007 or later (P = 0.029). Genetic testing identified 27 different variants for the SRD5A2 gene (30% novel, n = 8) and 18 for the HSD17B3 gene (44% novel, n = 8). Before 2002, most patients were initially assigned as females (95%, n = 19), but this proportion dropped for those born later (44%, n = 14; P < 0.001). The influence of initial genital appearance on these decisions seemingly decreased in the most recent years. Therapeutic interventions differed according to the sex of rearing. Ten percent (n = 2) patients requested female-to-male reassignment during adulthood.
This study showed, over the past two decades, a clear trend toward earlier diagnosis and assignment of affected newborns as males.
自分子诊断可用以来，研究2型5α-还原酶（SRD5A2）或3型17β-羟基类固醇脱氢酶（HSD17B3）缺乏症患者的诊断方法和临床管理变化。
从52例经分子诊断为SRD5A2缺乏症（n = 31）或HSD17B3缺乏症（n = 21）患者的病历中检索临床、实验室和治疗数据。对1994 - 2020年评估年龄和初始性别指定的时间趋势进行定性分析。根据出生年份比较两组患者的分子诊断年龄。
58%（n = 30）的患者在围产期被诊断，33%（n = 17）在婴儿期被诊断，9%（n = 5）在青少年期或成年期被诊断。在研究期间，患者初次评估和诊断时的年龄明显下降。2007年以前出生的患者确诊时的中位（范围）年龄为10.5（0 - 53.2）岁，2007年或以后出生的患者为0.4（0 - 9.3）岁（P = 0.029）。基因检测确定SRD5A2基因有27种不同变异（30%为新变异，n = 8），HSD17B3基因有18种不同变异（44%为新变异，n = 8）。2002年以前，大多数患者最初被指定为女性（95%，n = 19），但后来出生的患者这一比例下降（44%，n = 14；P < 0.001）。近年来，初始生殖器外观对这些决定的影响似乎有所下降。治疗干预因抚养性别而异。10%（n = 2）的患者在成年期要求从女性重新指定为男性。
本研究表明，在过去二十年中，受影响新生儿早期诊断并指定为男性的趋势明显。
