17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is expressed mostly in the testes and converts the inactive Δ4-androstenedione (A) to testosterone (T). 17β-HSD3 deficiency is a rare autosomal recessive disorder and the most common testosterone biosynthesis defect leading to 46,XY Disorders of Sex Development (DSD). To date, more than 40 mutations of HSD17B3 have been reported. 46,XY patients with 17β-HSD3 deficiency would present with wide variable external genitalia (Sinnecker Type 5 → Tip 2, but mostly Sinnecker Type 4,5. The patient was referred to our practise at the age of one year due to atypical external genitalia. Patients parents were first-degree cousins. On physical examination displayed nearly complete female external genitalia and bilateral mass in her groin (Prader stage 2 & Sinnecker Type 4). Chromosomal analysis revealed a 46,XY karyotype, therefore patient diagnosed 46, XY DSD. In laboratory, T/A ratio was less than 0.8. When the patient was seven years old, his newborn twin sisters referred to us due to the same clinical condition, external genitalia and laboratory parameters. Their chromosomal analysis revealed a 46,XY karyotype too. We detected a de novo homozygous c.577C>T (p.P193S) mutation in HSD17B3 gene in three siblings. Parents and one brother were heterozygous for this mutation. Furthermore, same homozygous mutation was detected in a sister with 46, XX chromosomes without any complaint. In slico variant analysis, DANN Score was 0.9989 (Disease causing). We reported 3 siblings patients with 17β-HSD3 deficiency. Ambiguous genital phenotype, 46,XY male karyotype and the ratio of testosterone vs androstenedione less than 0.8 could suggest the diagnosis.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology