Abstract 189: Endocrine evaluation dilemmas in 46XY DSD with excised gonads: Compound heterozygous 17β-hydroxysteroid dehydrogenase type-3 novel mutation

Background: 17-HSD-3 deficiency is autosomal recessive, rare cause of 46XY, DSD. The diagnosis is often missed in early childhood due to subtle features, and the usual presentation is at puberty with primary amenorrhea and features of virilisation. Herein we describe 34-year 46XY female who was never diagnosed and found to have compound heterozygous mutations in exon 1 and exon 9 in HSD17B3 gene by genetic testing. Case Detail: Patient was first-born to a non-consanguineously married couple, term delivery with typical female external genitalia, and reared as female. There was history of right-sided inguinal hernia repair at 3 years of age. Breast development started at 15 years of age, along with deepening of voice and appearance of facial and body hair at 16-17 years. Initial evaluation by a Gynaecologist at 26 years of age for primary amenorrhea revealed a blind vagina, clitoromegaly, bilateral palpable gonads in inguinal region with 46XY karyotype. MRI revealed testes in inguinal canals and absence of Mullerian structures. No endocrine evaluation was done at this stage, and she underwent bilateral orchidectomy followed by estrogen supplementation. The patient first consulted us 8-years later, at 34 years of age. Since she had undergone bilateral orchidectomy, interpretation of hormonal evaluation including hCG-stimulation, was not feasible. Genetic sequencing revealed compound heterozygous mutations for c.128_131 del at exon 1 and c.644A>T novel mutation at exon 9 in HSD17B3 gene. The patient wanted to continue with the assigned female sex, and was continued on estrogen therapy along with genetic counselling. Discussion: Mutation in HSD17B3 is rare cause of 46XYDSD. Usually reared as female, these patients come to medical attention because of inguinal hernia or labioscrotal swelling in childhood or primary amenorrhea along with variable degree of virilization in pubertal age group. Without specific endocrine evaluation, it may be overlooked as androgen insensitivity and 5-alpha-reductase deficiency due to clinical similarities. Basal and stimulated hormonal evaluation of hormonal precursors and metabolites can provide valuable information about the level of defect. Confirmatory molecular mutation analysis is often required, particularly in the setting of gonadectomy, as was the case in our patient. A total of 70 different mutation in the HSD17B3 gene has been reported to date The p.Phe43CysfsTer9 mutation at exon 1 identified in our patient has previously been reported, but p.Glu215Val mutation at exon 9 has not been previously reported and is a novel mutation.