46 XY DISORDERS OF SEXUAL DEVELOPMENT (DSD) CAUSED BY A RARE MUTATION OF THE 17 beta HYDROXYSTEROID DEHYDROGENASE TYPE 3 GENE (HSD17B3)

Similar phenotypes in 46,XY DSD have different etiopathogenesis. Androgen (A) synthesis are rare respect to A action/metabolism defects. The most frequent cause in the former group is a mutation of HSD17B3, gene encoding for an enzyme (17BHSD3) converting delta4-androstenedione (D4) into testosterone (T). Homozygotes/compound heterozygotes have testes, male wolffian structures, completely female (F) or mildly virilized external genitalia (EG). Pts with not palpable testes may appear as F, but they virilize at puberty for the increase in serum T. Our patient (12-yrs-old. 46,XY) for FEG at birth was raised as girl until puberty, when clitoris enlargement (> 4 cm) and male pattern of body hair and timbre of voice appeared. The EG corresponded to Prader stage III. Pelvic echography: two hypoechogenic ovoid masses in inguinal regions, compatible with testes, no Müllerian structures, echogenic structure (20x5mm) like hypoplastic uterus, posteriorly to the bladder. T synthesis: reduced before (3.3 ng/ml) and after (4.0 ng/ml) HCG test; baseline D4/t ratio: 5.75 (nv < 0.85); iv ACTH test: basal and peak D4>10 ng/ml. A homozygous C to T mutation was found at nucleotide position 238 in exon 3, resulting in the change from R80W. Both parents were heterozygous for this mutation. Bilateral gonadectomy, clitoridoplasty and surgical correction of EG in F sense were performed because the F gender role behaviour and gender identity. Histologic examination: testicular tissue (Sertoli cells, spermatogonia in seminiferous tubules, normal interstitial stroma, hyperplastic Leydig cells), and normal epididymi. Vagina length 2.5 cm. In conclusion, early diagnosis of 17betaHSD3 deficiency is frequently difficult, because clinical signs may be mild or absent until puberty and biochemichal parameters are not always diagnostic. Thus, the endocrine evaluation is the first step in the diagnosis of 46XY, DSD, but in all forms, particularly in pts suspected of a 17betaHSD3 deficiency, mutation analysis of the coding gene is irreplaceable to confirm the diagnosis.