Practical approach to steroid 5alpha-reductase type 2 deficiency.

Area of Science:

• Endocrinology
• Genetics
• Sexual Differentiation

Background:

• Steroid 5-alpha-reductase type 2 (5α-RD2) is crucial for converting testosterone to dihydrotestosterone.
• Mutations in the SRD5A2 gene cause 5α-RD2, an autosomal recessive disorder impacting sexual development in 46,XY individuals.
• Phenotypes range from female-appearing to ambiguous genitalia at birth, with virilization and potential gender identity changes at puberty.

Purpose of the Study:

• To review the literature on 5α-RD2.
• To provide clinicians with guidance for managing patients with 5α-RD2.
• To highlight the importance of early diagnosis and appropriate gender assignment.

Main Methods:

• Literature review of studies on 5α-RD2.
• Analysis of reported mutations in the SRD5A2 gene.
• Comparison of 5α-RD2 phenotypes with other disorders causing 46,XY DSD.

Main Results:

• Over 40 mutations in the SRD5A2 gene have been identified across all five exons.
• Phenotype-genotype correlations for 5α-RD2 are not well-established.
• Newborn phenotypes of 5α-RD2 can be indistinguishable from partial androgen insensitivity syndrome (PAIS) or 17β-HSD3 deficiency.

Conclusions:

• Steroid 5α-RD2 should be considered in the differential diagnosis of newborns with 46,XY disorders of sex development (DSD).
• Biochemical and molecular studies in infancy are essential for diagnosis before gender assignment or surgery.
• Patients with 5α-RD2 should be considered male at birth.