ESPE Abstracts (2014) 82 P-D-3-1-955

Severe Undervirilisation in a 46,XY Case due to a Novel Mutation in HSD17B3 Gene

Ayfer Alikasifoglua, Dogus Vurallia, Olaf Hiortb, E Nazli Gonca, Z Alev Ozona & Nurgun Kandemira

aDepartment of Pediatric Endocrinology, Hacettepe University, Ankara, Turkey; bDivision of Pediatric Endocrinology and Diabetes, University of Lübeck, Lübeck, Germany

Background: 17-β-hydroxysteroid dehydrogenase 3 (17-β-HSD3) deficiency is a rare disorder of sex development due to impaired conversion of androstenedione to testosterone. Children with 46,XY karyotype often have female appearing external or ambiguous genitalia at birth. At the time of puberty, virilisation can occur. Therefore 46,XY patients with HSD17B3 gene defects should be raised as male.

Objective and hypotheses: When a child with 46,XY karyotype present with female appearing external or ambiguous genitalia and there is impaired conversion of androstenedione to testosterone, 17-β-HSD3 deficiency must be kept in mind.

Method: A case with 17-β-HSD3 deficiency with a novel mutation is presented.

Results: One year old girl was referred with the complaint of swelling in the right inguinal area. The parents were first cousins. In physical examination bilateral gonads were palpable in inguinal regions. She had a fallus of 1.5 cm and vaginal and urethral orifices were separate. The karyotype was 46 XY. On ultrasonography no Mullerian structures could be seen and gonads were in the inguinal canal. Following injection of 1500 U/m2 hCG for 3 days testosterone, dihydrotestosterone and androstenedione levels were 29.9 ng/dl, 82.4 pg/ml and 2.78 ng/ml respectively. Testosterone/dihydrotestosterone ratio was 3.6 which was normal. Testosterone/androstenedione ratio was found to be 0.107 (n>0.8) suggesting 17-β-HSD3 deficiency. Molecular analysis of the HSD17B3 gene showed a homozygous mutation c.761_762delAG corresponding to p.E254VfsX10 in the patient and both parents were heterozygous. A deletion of two nucleotides in exon 10 was found, which lead to a frameshift and subsequently to premature termination within the protein. This deleterious mutation caused 17-β-HSD-3 deficiency in this patient. The parents did not accept sex reassignment into male and bilateral gonadectomy was performed. The histopathology of gonads were consistent with testis and spermatic cord.

Conclusion: A novel mutation p.E254VfsX10 in HSD17B3 gene caused severe undervirilisation in a 46,XY patient. Early diagnosis is crucial for appropriate sex of rearing.

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