Introduction: Deficiency of 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) enzyme encoded by HSD17B3 is a rare cause of disorders of sex development (DSD). The phenotype associated with 17β-HSD3 deficiency in 46, XY individuals is variable, ranging from predominantly male external genitalia with micropenis and hypospadias to completely female external genitalia. The diagnosis and management of this enzymatic defect is very challenging.
Case Presentation: Case 1. A 1.6-year-old girl born to first-cousin parents presented after surgical repair of bilateral inguinal hernia, where testes with Wolffian duct elements were identified in the inguinal pouches. Karyotyping revealed a 46, XY male genotype. LH level was mildly elevated (3.1 mIU/mL). hCG stimulation test demonstrated a subnormal increase in testosterone level and a low stimulated T/Δ4A ratio of 0.44 consistent with HSD17B3 mutation. Her parents decided to raise her as a girl and therefore, bilateral gonadectomy was performed. Case 2 (aunt of case 1). A 27-year-old female presented with primary amenorrhea. On examination, she had a male appearance with severe hirsutism, male hair balding, clitoromegaly of 3 cm and bilateral palpable inguinal mass of 2 mL. Abdominal computed tomography scan confirmed two abdominal masses. Karyotype was 46, XY. Elevated LH of 24 mIU/L and FSH of 36 mIU/mL with elevated testosterone of 3 ng/mL (normal range for male, 2.48.3) were found. She decided to continue as a female and express her female gender identity, and therefore bilateral gonadectomy with vaginoplasty were undertaken. Gonadal biopsy revealed Sertoli cells without spermatogenesis with diffuse hyperplasia of Leydig cells and hyaline fibrosis of the tubule walls. In the left testis, a non-invasive seminoma of 1.7 cm was shown. The phenotype of both patients with low T/Δ4A ratio (less than 0.8) raised the diagnosis of 17β-HSD3 deficiency. Sequencing of HSD17B3 identified a novel homozygous missense mutation, Thr81Pro, in both patients. The challenging nature of this diagnosis, and the difficulties involved in sex assignment decisions and gender dysphoria in 17β-HSD3 deficiency will be discussed. Our findings emphasize the importance of high awareness of this rare enzymatic defect and the role of molecular analysis in early diagnosis, as well as in the management and sex assignment decision in 17β-HSD3 deficiency.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology