46,XY disorder of sex development (DSD) due to 17β-hydroxysteroid dehydrogenase type 3 deficiency

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 165; no. Pt A; pp. 79 - 85
• Main Authors: Mendonca, Berenice B., Gomes, Nathalia Lisboa, Costa, Elaine M.F., Inacio, Marlene, Martin, Regina M., Nishi, Mirian Y., Carvalho, Filomena Marino, Tibor, Francisco Denes, Domenice, Sorahia
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.01.2017
• Subjects: 17-Hydroxysteroid Dehydrogenases - deficiency; 17-Hydroxysteroid Dehydrogenases - genetics; 17β-Hydroxysteroid dehydrogenase 3; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - deficiency; 3-Oxo-5-alpha-Steroid 4-Dehydrogenase - genetics; 46, XY Disorders of Sex Development - genetics; 46,XY DSD; Adolescent; Adult; Ambiguous genitalia; Androgen-Insensitivity Syndrome - genetics; Child; Child, Preschool; Chromosomes, Human, X - genetics; Chromosomes, Human, Y - genetics; Disorders of Sex Development - genetics; Exons; Female; Gender role; Genetic Testing; Genotype; Germ cell tumor; Homozygote; HSD17B3 gene; Humans; Hypospadias - genetics; Male; Mutation; Phenotype; Retrospective Studies; Steroid Metabolism, Inborn Errors - genetics; Testosterone synthesis defect; Virilism - genetics; Young Adult; Germ cell tumor; 46,XY DSD; Testosterone synthesis defect; 17β-Hydroxysteroid dehydrogenase 3; HSD17B3 gene; Ambiguous genitalia; Gender role
• ISSN: 0960-0760; 1879-1220; 1879-1220
• DOI: 10.1016/j.jsbmb.2016.05.002

•17β-HSD3 deficiency should be suspected in females with inguinal hernias or mild clitoromegaly in infancy or early childhood as well as virilization at puberty associated with low T/A ratio.•Some affected children have normal T/A ratio and the diagnosis of 17β-HSD3 deficiency is performed by molecular analysis of HSD17B3.•Molecular genetic testing confirms the diagnosis and provides the orientation for genetic counseling.•Almost half of the patients changed from female to male social sex in adulthood.•In male social sex patients, testes can be safely maintained, as long as they are positioned inside the scrotum. 17β-hydroxysteroid dehydrogenase 3 deficiency consists of a defect in the last phase of steroidogenesis, in which androstenedione is converted into testosterone and estrone into estradiol. External genitalia range from female-like to atypical genitalia and most affected males are raised as females. Virilization in subjects with 17β-HSD3 deficiency occurs at the time of puberty and several of them change to male social sex. In male social sex patients, testes can be safely maintained, as long as they are positioned inside the scrotum The phenotype of 46,XY DSD due to 17β-HSD3 deficiency is extremely variable and clinically indistinguishable from other causes of 46,XY DSD such as partial androgen insensitivity syndrome and 5α-reductase 2 deficiency. Laboratory diagnosis is based on a low testosterone/androstenedione ratio due to high serum levels of androstenedione and low levels of testosterone. The disorder is caused by a homozygous or compound heterozygous mutations in the HSD17B3 gene that encodes the 17β-HSD3 isoenzyme leading to an impairment of the conversion of 17-keto into 17-hydroxysteroids. Molecular genetic testing confirms the diagnosis and provides the orientation for genetic counseling. Our proposal in this article is to review the previously reported cases of 17β-HSD3 deficiency adding our own cases.