Abstract 24: NR5A1 mutation: A single centre experience from South India

Background: Inactivating mutations involving Nuclear receptor subfamily 5 group A member (NR5A1) or steroidogenic factor 1 (SF1), is increasingly being recognized as an important cause of 46XY DSD and rarely 46XX DSD. Myriad of presentations include undervirilized male with or without peripubertal virilization, ovotesticular DSD and premature ovarian failure. With the widespread availability of genetic testing it has been found that it constitutes atleast 15% of cases of 46XY DSD. Aims and Objective: To describe the clinical presentation of a series of patients with genetically confirmed SF1 mutations from a south Indian tertiary care centre. Result: Extreme undervirlization was noted in one subject whereas prepubertal virilization was noted in two subjects reared as females. Hormonal investigations revealed various varying degrees of Sertoli cell dysfunction (elevated FSH and low inhibin B), poor Leydig cell function in prepubertal subjects (HCG stimulated testosterone <0.087 nmol/l) and apparent recovery of Leydig cell function in peripubertal period (2.04 & 2.94 ng/ml). Exon Variants-Exon 2 c.58G>T(p.Val20Leu), Exon 5 c.940delinsACGGCAAGG (p.Gin314ThrfsTer23) and Exon 3 c.223A>C (p.Thr75Pro) were noted . Conclusion: 46XY DSD due to inactivating NR5A1 variants can present in unusual ways characterized by extreme undervirlization at birth with apparent recovery of Leydig cell function later on.