ESPE Abstracts (2022) 95 P1-183

1Hospices Civils de Lyon, Bron, France; 2Université Claude Bernard Lyon 1, Lyon, France; 3Centre Hospitalier Régional et Universitaire de Besançon, Besançon, France; 4Centre Hospitalier Valenciennes, Valenciennes, France; 5Centre Lyonnais d’Urologie Bellecour, Lyon, France

Background: Steroidogenic Factor 1 (SF-1), encoded by NR5A1 (Nuclear receptor subfamily 5 group A member 1) gene, is a transcriptional factor that is primordial for adrenal and gonadal organogenesis. Pathogenic variants of NR5A1 are responsible for a wide spectrum of phenotypes with autosomal dominant inheritance, from adrenal insufficiency to gonadal dysgenesis and oligospermia-azoospermia in 46,XY patients.

Objective: Preservation of fertility in these patients remains challenging. The aim was to offer fertility preservation at the end of puberty in a patient with a new pathogenic NR5A1 variant.

Case report: The patient was born from non-consanguineous parents, with a disorder of sex differentiation: a small genital bud of 6x4mm, a perineal hypospadias, gonads in the left labrum and the right inguinal respectively. The morphological studies did not show any uterus or vagina. The karyotype was 46,XY. AMH levels were low at 58 pmol.L-1 the first day of life then 100 pmol.L-1 at the minipuberty. Testosterone level was low at 0.9 nmol.L-1 at 12-h of life, and Testosterone after hCG stimulation increased properly to 10.8 nmol.L-1. The child was raised as a boy. During endocrine monitoring, he received androgen therapy (11 injections of testosterone enanthate) for one year. He underwent a surgical treatment for his hypospadias at one year old and for testicular lowering at 7 years old. He was treated by triptorelin for central precocious puberty from 9.5 years old to 11 years old. From 13 to 15 years old, androgen therapy by testosterone enanthate was established to improve penis size prognosis. Genetic study, performed at 15 years old, identified the new frameshift variant NM_004959.5(NR5A1):c.207del p.(Phe70Serfs*5) at an heterozygous state. Therefore, he was addressed for fertility preservation. At 16 years old, testicular volume was 6 ml bilaterally; AMH and inhibin B levels were low (2.6 pmol.L-1 and 9.0 ng.mL-1 respectively). No sperm cells could be retrieved from three semen collection between 16 and 17 years old. The patient accepted a testicular biopsy for testicular sperm extraction. The procedure was performed at 18 years old and no sperm cells were found. Histological analysis revealed a severe hypo-spermatogenesis with an aspect of histological mosaicism (seminiferous tubules either atrophic, either with Sertoli cells only or with arrest of spermatogenesis at the spermatocyte stage).

Conclusion: We report a case with a new NR5A1 variant. The fertility preservation protocol proposed at the young age before parental project did not allow any sperm retrieval.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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