Pubertal Development in
17Beta-Hydroxysteroid Dehydrogenase Type 3 Deficiency

Abstract

Background: 17β-hydroxysteroid dehydrogenase (17β-HSD) type 3 deficiency is an autosomal recessive disorder with diminished testosterone synthesis and consequently underandrogenisation. 46,XY patients with 17β-HSD type 3 deficiency are often assigned a female sex at birth but have a high virilisation potential at the time of puberty. Methods: We studied four 46,XY patients with 17β-HSD type 3 deficiency at puberty with regard to the underlying mutations, the hormone values, and the clinical findings. Results: Three patients were initially assigned a female sex and 1 was assigned a male sex. All had relevant mutations in the HSD17B3 gene. The 2 patients with deleterious mutations had lower testosterone values at the time of puberty than the patients with possible residual activity of 17β-HSD type 3. One of the latter patients changed to male gender. Conclusion: All 4 patients with 17β-HSD type 3 deficiency synthesized relevant amounts (>0.7 µg/L) of testosterone at puberty, which lead to variable androgenisation. In patients with presumable residual activity of the mutated enzyme, testosterone values in the male reference range can be achieved, thereby inducing male pubertal development. These patients should possibly be assigned a male sex. Any surgical intervention should be avoided until the patients are old enough to consider their options of medical and surgical intervention.

Disorders of Sex Development: Classification, Review, and Impact on Fertility

“…This enzyme (17β-oxireductase) is also required for the conversion of estrone to estradiol (E2). 17β-HSD-3 deficiency is an autosomal recessive disorder with decreased T synthesis and, consequently, subandrogenization; hence, 46,XY patients with this deficiency are often assigned a female sex at birth, although they have a high potential for virilization at puberty [125]. The diagnosis can easily be lost in early childhood, as the clinical presentation can be subtle [126].…”

Patients with disorders of sex development

“…In girls, the most common presentation is as primary amenorrhea, with or without breast development and with or without virilization. 17) Evaluation should be initiated at 13 years of age if there is no pubertal development and at 16 years if breast development has progressed normally but there is amenorrhea. In girls with one or more signs of virilization, such as clitoromegaly, excessive acne, facial hair, and voice change along with a lack of secondary sexual development, evaluation may be considered before the age of 13 years.…”

“…In girls, the most common presentation is as primary amenorrhea, with or without breast development and with or without virilization [ 17 ]. Evaluation should be initiated at 13 years of age if there is no pubertal development and at 16 years if breast development has progressed normally but there is amenorrhea.…”

Male pseudohermaphroditism: A case study of 46,XY disorder of sexual development using whole‐exome sequencing

“…Besides, AIS may also be related to a deficit in AR coactivators caused by mutations in the relevant genes, such as NR5A1 encoding the steroidogenic factor‐1 protein, 4 which among other functions promotes the transcription of steroidogenic enzymes and steroidal receptors. Other possible molecular causes of the DSD are related to deficiencies in key enzymes controlling the androgens' production associated with various deleterious variants in the relevant genes: Cytochrome P450 17α‐hydroxylase ( CYP17A1 ) and 17β‐hydroxysteroid dehydrogenase ( HSD17B3 ), essential for steroidogenesis, and 5α‐reductases ( SRD5A1 and SRD5A2 ), necessary for the conversion of testosterone into its more potent form, dihydrotestosterone 5‐8 . These deficiencies may manifest in phenotypes identical to CAIS or severe PAIS.…”

“…Other possible molecular causes of the DSD are related to deficiencies in key enzymes controlling the androgens' production associated with various deleterious variants in the relevant genes: Cytochrome P450 17α-hydroxylase (CYP17A1) and 17β-hydroxysteroid dehydrogenase (HSD17B3), essential for steroidogenesis, and 5α-reductases (SRD5A1 and SRD5A2), necessary for the conversion of testosterone into its more potent form, dihydrotestosterone. [5][6][7][8] These deficiencies may manifest in phenotypes identical to CAIS or severe PAIS.…”