Pubertal Development in 17Beta-Hydroxysteroid Dehydrogenase Type 3 Deficiency

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.


Assessing the health-related management of people with differences of sex development

Purpose Health care requirements and perception of people with differences of sex development (DSD) have changed enormously since the "Chicago Consensus Conference" in 2005. Therefore, new standards of care and evaluation of care have to be developed. Methods We summarize the social and legal approach to care for DSD during the last two decades and report the main results of European research activities. Results The last two decades were accompanied by legal and societal discussion regarding how to deal with a nonbinary concept of sex. This leads to the necessity to assess health care requirements for individuals with DSD in an objective manner. We briefly review the results of the recently funded European research projects dealing with health-related issues in DSD like EU COST Action DSD, I-DSD, and dsd-LIFE, and address the compilation of quality indicators that will be needed to benchmark health care provision and health care-related outcomes. Conclusions The benchmarking process has to be implemented among health care providers for individuals with DSD within the European Reference Networks for Rare Conditions