J Pediatr Endocr Met 2015; 28(7-8): 961–965 *Corresponding author: Assoc. Prof. Dr. Korcan Demir, Division of Pediatric Endocrinology, Dr. Behçet Uz Children’s Hospital, Çocuk Endokrinolojisi Bölümü, Dr. Behçet Uz Çocuk Hastanesi, Sezer Doğan Sokak No 11, 35210, Konak, İzmir, Türkiye, Phone: +90 232 411 6318, Fax: +90 232 489 2315, E-mail: korcandemir@gmail.com Melek Yıldız, Özlem Nalbantoğlu Elmas, Hüseyin Anıl Korkmaz, Selma Tunç and Behzat Özkan: Division of Pediatric Endocrinology, Dr. Behçet Uz Children’s Hospital, İzmir, Turkey Özgür Olukman: Division of Neonatology, Dr. Behçet Uz Children’s Hospital, İzmir, Turkey Filiz Hazan: Division of Medical Genetics, Dr. Behçet Uz Children’s Hospital, İzmir, Turkey Keramettin Uğur Özkan: Division of Pediatric Surgery, Dr. Behçet Uz Children’s Hospital, İzmir, Turkey Patient report Korcan Demir*, Melek Yıldız, Özlem Nalbantoğlu Elmas, Hüseyin Anıl Korkmaz, Selma Tunç, Özgür Olukman, Filiz Hazan, Keramettin Uğur Özkan and Behzat Özkan Two different patterns of mini-puberty in two 46,XY newborns with 17 β-hydroxysteroid dehydrogenase type 3 deficiency Abstract: We report two newborns with female exter- nal genitalia and bilateral inguinal swelling who were diagnosed with 17β-hydroxysteroid dehydrogenase type 3 deficiency, a rare cause of 46,XY disorder of sexual development. The first case had normal clitoral size and vaginal and urethral openings, palpable gonads in the inguinal region, low testosterone, and low levels of basal and GNRH-stimulated gonadotropin. The second case had similar external genitalia, low testosterone but borderline basal and normal stimulated gonadotropin levels. Low tes- tosterone/androstenedione ratios (0.22 and 0.24, respec- tively; normal,  > 0.8) after human chorionic gonadotropin stimulation indicated 17β-hydroxysteroid dehydrogenase type 3 deficiency. HSD17B3 sequencing revealed a homozy- gous novel mutation (c.464A > C, p.H155P) in exon 6 in the first case and homozygous c.239G > A (p.R80Q) in exon 3 in the second. Keywords: 17β-HSD3 deficiency; HSD17B3; DSD; gender reassignment; orchiectomy. DOI 10.1515/jpem-2014-0365 Received August 27, 2014; accepted February 11, 2015; previously published online April 16, 2015 Introduction At birth, physical examination is not informative enough to tell the parents about the sex of their baby in one of nearly 5000 newborns (1). However, features of disorders of sex development (DSD) are not limited to ambiguous genitalia. Subjects with 46,XY DSD might have apparently female external genitalia at birth and remain unnoticed until they present with associated problems, including adrenal failure, lack of pubertal development, and virili- zation during puberty (2). Testicular 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) is responsible for the conversion of andros- tenedione to testosterone, which is necessary for normal masculinization of male genitalia in utero. The deficiency of this enzyme is a rare cause of 46,XY DSD, except in the Gaza Strip Arab population and occurs due to autosomal recessively inherited HSD17B3 mutations (1, 3). Affected individuals mostly present with female external genitalia with or without clitoromegaly, labial fusion, blind ending vagina, and inguinal testes with Wolffian duct derivatives. Disease spectrum ranges from completely external female genitalia in the majority to micropenis and hypospadias (1, 2). Patients with 17β-HSD3 deficiency are mostly unno- ticed and are thus raised as females. During puberty, gonadotropin surge stimulates excessive production of testosterone both by gonadal and probably extragonadal conversion of androstenedione to testosterone catalyzed by a family of 17β-HSD3 isoenzymes, resulting in viriliza- tion. Subsequently, issue of gender reassignment from female to male emerges, which is reported to be 39% to 64% (1). Diagnosis is possible with a low serum testos- terone/androstenedione (T/A) ratio after human chori- onic gonadotropin (hCG) stimulation (normal,  > 0.8) and genetic analysis (4). Although many cases of 17β-HSD3 deficiency diagnosed in infancy have been reported to date, their hormonal data with respect to mini-puberty Brought to you by | University of Queensland - UQ Library Authenticated Download Date | 8/16/15 5:10 PM