title: 46,XY disorder of sex development (DSD) due to 17β-hydroxysteroid dehydrogenase type 3 deficiency.
abstract: 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.
authors.affiliation: Developmental Endocrinology Unit, Hormone and Molecular Genetics Laboratory (LIM/42), Endocrinology Division, Internal Medicine Department, Medical School, University of São Paulo, Brazil. Electronic address: beremen@usp.br.
authors.forename: Berenice B
authors.initials: BB
authors.lastname: Mendonca
authors.affiliation: Developmental Endocrinology Unit, Hormone and Molecular Genetics Laboratory (LIM/42), Endocrinology Division, Internal Medicine Department, Medical School, University of São Paulo, Brazil.
authors.forename: Nathalia Lisboa
authors.initials: NL
authors.lastname: Gomes
authors.affiliation: Developmental Endocrinology Unit, Hormone and Molecular Genetics Laboratory (LIM/42), Endocrinology Division, Internal Medicine Department, Medical School, University of São Paulo, Brazil.
authors.forename: Elaine M F
authors.initials: EM
authors.lastname: Costa
authors.affiliation: Developmental Endocrinology Unit, Hormone and Molecular Genetics Laboratory (LIM/42), Endocrinology Division, Internal Medicine Department, Medical School, University of São Paulo, Brazil.
authors.forename: Marlene
authors.initials: M
authors.lastname: Inacio
authors.affiliation: Developmental Endocrinology Unit, Hormone and Molecular Genetics Laboratory (LIM/42), Endocrinology Division, Internal Medicine Department, Medical School, University of São Paulo, Brazil.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: Developmental Endocrinology Unit, Hormone and Molecular Genetics Laboratory (LIM/42), Endocrinology Division, Internal Medicine Department, Medical School, University of São Paulo, Brazil.
authors.forename: Mirian Y
authors.initials: MY
authors.lastname: Nishi
authors.affiliation: Pathology Department, Medical School, University of São Paulo, Brazil.
authors.forename: Filomena Marino
authors.initials: FM
authors.lastname: Carvalho
authors.affiliation: Urology Division, Surgery Department, Medical School, University of São Paulo, Brazil.
authors.forename: Francisco Denes
authors.initials: FD
authors.lastname: Tibor
authors.affiliation: Developmental Endocrinology Unit, Hormone and Molecular Genetics Laboratory (LIM/42), Endocrinology Division, Internal Medicine Department, Medical School, University of São Paulo, Brazil.
authors.forename: Sorahia
authors.initials: S
authors.lastname: Domenice
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000172:deficiency / Q000235:genetics; D000293:Adolescent; D000328:Adult; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D041322:Chromosomes, Human, Y / Q000235:genetics*; D058490:Disorder of Sex Development, 46,XY / Q000235:genetics; D012734:Disorders of Sex Development / Q000235:genetics*; D005091:Exons; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007021:Hypospadias / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies; D043202:Steroid Metabolism, Inborn Errors / Q000235:genetics; D014770:Virilism / Q000235:genetics; D055815:Young Adult
chemical_list: D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase
keywords: 17β-Hydroxysteroid dehydrogenase 3; 46,XY DSD; Ambiguous genitalia; Gender role; Germ cell tumor; HSD17B3 gene; Testosterone synthesis defect