ESPE Abstracts

Introduction: Pathogenetic mutations in the HSD17B3, located on chromosome 9q22, lead to 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) isoenzyme deficiency, etiopathogenetic for a disorder of sex development (DSD) with 46 XY karyotype and female phenotype at birth. 17β-HSD3 isoenzyme, expressed at testicular tissue, catalyzes the synthesis of testosterone from Δ4-androstenedione, allowing the correct development of male external genitalia during the fetal life; its deficiency results in the development of female external genitalia while maintaining male internal organs. Often at birth this condition is not diagnosed, seeking medical treatment during adolescence for primary amenorrhea and virilization.

Case report: A 13-year-old adolescent with Morris Syndrome diagnosed at birth, comes to our observation for virilization during puberty. At birth the patient presented female genitalia with a 46 XY karyotype at amniocentesis results. A diagnosis of Complete Insensitivity to Androgens (CAIS) has been performed and she was raised as a female. The parents didn’t search for a specialist care until puberty when the patient began to show virilization. Genetic investigations for CAIS, in particular the NGS panel associated with DSD, did not detect variants of pathological significance. Hormonal investigations showed low testosterone/androstenedione ratio (T/A ratio) 0,4 (normal range > 0,8). The HSD17B3 gene analysis revealed the presence in heterozygosis of two variants: c.221A>C, p.Asn74Thr in exon 3, absent in the international database, and c.227+4A>T in intron 3, classified as pathological. Parent’s HSD17B3 gene analysis showed c.221A>C, p.Asn74Thr in mother’s line and c.227+4A>T in father’s line. The patient was treated with GnRH-agonist to interrupt pubertal development and to reduce male virilization. She promptly has started psychological support that confirmed her female identity. She is followed by a multidisciplinary group to establish the correct surgical treatment.

Conclusions: 17β-HSD3 deficiency should always be taken into account in patients with DSD and 46XY karyotype, further genetical investigation at birth or at puberty in late diagnosis are mandatory for a correct management. Still an open question is the timing of the choice of gender identity and the consequent surgical intervention in adolescent age, at the moment not described.