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Université Pierre et Marie Curie, Sorbonne Université, Paris, France
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INSERM UMR_S933, Paris, France
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Université Pierre et Marie Curie, Sorbonne Université, Paris, France
INSERM UMR_S933, Paris, France
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Human 3 beta-hydroxysteroid dehydrogenase deficiency (3b-HSD) is a very rare form of congenital adrenal hyperplasia resulting from HSD3B2 gene mutations. The estimated prevalence is less than 1/1,000,000 at birth. It leads to steroidogenesis impairment in both adrenals and gonads. Few data are available concerning adult testicular function in such patients. We had the opportunity to study gonadal axis and testicular function in a 46,XY adult patient, carrying a HSD3B2 mutation. He presented at birth a neonatal salt-wasting syndrome. He had a micropenis, a perineal hypospadias and two intrascrotal testes. HSD3B2 gene sequencing revealed a 687del27 homozygous mutation. The patient achieved normal puberty at the age of 15 years. Transition from the paediatric department occurred at the age of 19 years. His hormonal profile under hydrocortisone and fludrocortisone treatments revealed normal serum levels of 17OH-pregnenolone, as well as SDHEA, ACTH, total testosterone, inhibin B and AMH. Pelvic ultrasound identified two scrotal testes of 21 mL each, without any testicular adrenal rest tumours. His adult spermatic characteristics were normal, according to WHO 2010 criteria, with a sperm concentration of 57.6 million/mL (N > 15), 21% of typical forms (N > 4%). Sperm vitality was subnormal (41%; N > 58%). This patient, in contrast to previous reports, presents subnormal sperm parameters and therefore potential male fertility in a 24-years-old patient with severe 3b-HSD deficiency. This case should improve counselling about fertility of male patients carrying HSD3B2 mutation.
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Département de Métabolomique Clinique, Hôpital Saint-Antoine, AP-HP Sorbonne Université, Paris, France
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Département de Métabolomique Clinique, Hôpital Saint-Antoine, AP-HP Sorbonne Université, Paris, France
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Université de Paris, INSERM, Institut IMAGINE, Hôpital Necker-Enfants Malades, AP-HP, Paris, France
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Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, Paris, France
Hôpital Armand Trousseau, AP-HP Sorbonne Université, Paris, France
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Département de Métabolomique Clinique, Hôpital Saint-Antoine, AP-HP Sorbonne Université, Paris, France
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Neonatal screening for congenital adrenal hyperplasia (CAH) faces many specific challenges. It must be done using a performant analytical approach that combines sensitivity and specificity to capture the potential causes of mortality during the first week of life, such as salt wasting and glucocorticoid deficiency. Here, we confirm that maternal inhaled corticosteroid intake during pregnancy is a possible cause of missed CAH diagnosis. Thanks to liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis, we were able to quantify endogenous steroid metabolites and also detect the presence of exogenous steroids in the dried blood spot of a newborn. Adding LC-MS/MS analysis as second-tier test, especially one that includes both 17-hydroxyprogesterone and 21-deoxycortisol measurements, would probably improve CAH diagnosis. In familial neonatal screening one could also look for maternal corticosteroid therapies that are hidden to prevent false-negative tests.
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Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de psychopathologie du développement, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Centre de biologie et pathologie Est, Service d’hormonologie, d’endocrinologie moléculaire et des maladies rares, Bron, France
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Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Centre de biologie et pathologie Est, Service d’hormonologie, d’endocrinologie moléculaire et des maladies rares, Bron, France
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Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service Endocrinologie Moléculaire et Maladies Rares, Bron, France
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Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de chirurgie Uro-viscérale et de Transplantation de l’Enfant, Bron, France
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Hospices Civils de Lyon, Groupement Hospitalier Est, Service d’endocrinologie, Bron, France
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Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
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Université Claude Bernard, Lyon, France
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Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Université Claude Bernard, Lyon, France
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Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de chirurgie Uro-viscérale et de Transplantation de l’Enfant, Bron, France
Université Claude Bernard, Lyon, France
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Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de chirurgie Uro-viscérale et de Transplantation de l’Enfant, Bron, France
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Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
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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.
