5α-reductase deficiency type 2 (5αRD2) is the second most common cause of 46, XY disorders of sex development. The 5α-reductase type 2 isozyme, which is encoded by the SRD5A2 gene , catalyzes the conversion of testosterone (T) to dihydrotestosterone (DHT). This study aimed to evaluate the clinical, laboratory, and molecular characteristics of patients with 5αRD2.

We retrospectively analyzed the clinical, laboratory, and genetic features of thirteen patients diagnosed with 5αRD2. Age, gender assignment, presenting features, hormonal profiles, and SRD5A2 variants were evaluated.

The median age of the patients at diagnosis was 4.16 years (IQR: 0.63-10.73 years) (range: 1 month – 14.4 years). At presentation, two patients were in mini-puberty, seven were prepubertal, and four were pubertal. All patients were genetically 46,XY; however, their assigned gender at presentation differed. Gender was assigned as male in 77% of cases and as female in 23% of cases. The most common presenting feature was micropenis. The median baseline and stimulated T/DHT ratios were 6.7 (IQR: 5.3-33) and 61.7 (IQR: 32.18-104.73), respectively. Molecular analysis revealed four different variants of the SRD5A2 gene; homozygous deletion of exon 1, c.193G > C (p.Ala65Pro), c.578A > G (p.Asn193Ser) and c.586G > A (p.Gly196Ser). Clinical features and hormonal data were compared between patients with missense variants and those with homozygous deletion of exon 1. The frequencies of hypospadias and cryptorchidism, as well as baseline T/DHT ratios, were similar between the groups. However, stimulated T/DHT ratios were higher in patients with deletion of exon 1 .

This study provides valuable insights into the clinical and molecular spectrum of 5αRD2. To the best of our knowledge, this is the first report presenting a large family with a homozygous deletion of exon 1 in the SRD5A2 gene.