3β-Hydroxysteroid dehydrogenase type-2 deficiency: Our experience and gonadal function-focused systematic review.

PURPOSE: In 3β-Hydroxysteroid dehydrogenase type-2 (3β-HSD2) deficiency, the gonadal phenotypic spectrum and its correlation with genotype are unclear. We describe our center’s experience and perform a systematic review. METHODS: Retrospective record review of five 3β-HSD2 deficiency probands from our center, along with per-patient data analysis of reported probands, was conducted to understand the genotype and gonadal phenotype correlation. Probands were subgrouped based on karyotype and residual enzyme activity (REA) of the genetic variant. RESULTS: Of 128 probands, subgroups were: 46,XY REA ≤ 2% (n = 66), > 2% (n = 21); 46,XX REA ≤ 2% (n = 29), > 2% (n = 12). All 46,XY probands had atypical genitalia; Sinnecker score ≤ 3 (93.1% vs. 88.2%) and cryptorchidism (13.7% vs. 23.5%) were similar between REA ≤ 2% and > 2% groups. 46,XY probands with pubertal data (REA ≤ 2%: 11, > 2%: 3) all had spontaneous puberty (gynecomastia: 3; early puberty: 2) with normal testosterone and gonadotropins (except two). Testicular adrenal rest tumors (TARTs) were reported in seven (median age 13 years); some retained spermatogenesis, and one case documented paternity. No testicular germ-cell tumors were reported. 46,XX probands with pubertal data (REA ≤ 2%: 12, > 2%: 4), all had spontaneous puberty except one (pubertal arrest). Median ages at thelarche (9.0 vs. 9.5 years) and menarche (12 vs. 11.5 years) were comparable between REA groups. Polycystic ovarian morphology (PCOM) was reported in seven, and infertility in one. CONCLUSION: No clear genotype–gonadal phenotype correlation was observed. Pubertal development and hormone secretion are largely preserved irrespective of REA. TARTs and PCOM are not uncommon. Fertility potential requires further studies.