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. 2023 Feb 14;12(3):e220227.
doi: 10.1530/EC-22-0227. Print 2023 Mar 1.

Changes in the clinical management of 5α-reductase type 2 and 17β-hydroxysteroid dehydrogenase type 3 deficiencies in France

Estelle Bonnet  1 , Mathias Winter  2   3   4 , Delphine Mallet  2   4 , Ingrid Plotton  2   5 , Claire Bouvattier  6 , Maryse Cartigny  7 , Laetiti Martinerie  8 , Michel Polak  9 , Anne Bachelot  10 , Frédéric Huet  11 , Sabine Baron  12 , Muriel Houang  13 , Sylvie Soskin  14 , Anne Lienhardt  15 , Jérôme Bertherat  16 , Cyril Amouroux  17 , Aurore Bouty  2   18 , Lise Duranteau  19 , Rémi Besson  20 , Alaa El Ghoneimi  21 , Dinane Samara-Boustani  22 , François Becmeur  23 , Nicolas Kalfa  24 , Françoise Paris  17 , François Medjkane  25 , Aude Brac de la Perrière  2   26 , Patricia Bretones  1   2 , Hervé Lejeune  27   28 , Marc Nicolino  1   2   28 , Pierre Mouriquand  2   18   28 , Daniela-Brindusa Gorduza  2   18 , Claire-Lise Gay  1   2
Affiliations

Changes in the clinical management of 5α-reductase type 2 and 17β-hydroxysteroid dehydrogenase type 3 deficiencies in France

Estelle Bonnet et al. Endocr Connect. .

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: This study showed, over the past two decades, a clear trend toward earlier diagnosis and assignment of affected newborns as males.

Keywords: 17β-hydroxysteroid dehydrogenase type 3 deficiency; 46,XY disorders of sex development; 5α-reductase type 2 deficiency; change in practices; sex assignment.

PubMed Disclaimer

Conflict of interest statement

Lise Duranteau is on the editorial board for Endocrine Connections but has not been involved with any editorial or peer review process of this manuscript.

Figures

Figure 1
Figure 1
Participant flowchart.
Figure 2
Figure 2
Sex of rearing and age at molecular diagnosis according to the year of birth.
Figure 3
Figure 3
Comparison between EMS at birth according to the assigned gender.
Figure 4
Figure 4
EMS according to the year of birth.
Figure 5
Figure 5
Genetic variants of patients with SRD5A2 deficiency.
Figure 6
Figure 6
Genetic variants of patients with HSD17B3 deficiency.
See this image and copyright information in PMC

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