Difficulties in diagnosis and treatment of 5α-reductase type 2 deficiency in a newborn with 46,XY DSD

Background/Aims: Steroid 5α-reductase deficiency (MIM*607306) caused by mutations in the SRD5A2 gene is characterized by a predominantly female phenotype at birth and significant virilization at puberty. The undermasculinization at birth results from low dihydrotestosterone (DHT) levels during fetal development as the type 2 isoenzyme activity is reduced. In puberty, when the type 1 isoenzyme activity increases, significant virilization occurs. Most 46,XY individuals with 5α-reductase 2 deficiency develop a male gender identity. Case Report and Results: We present a case with a predominantly female phenotype and ambiguous external genitalia but a normal 46,XY karyotype. Plasma steroid analysis after β-hCG stimulation at 8 days of age revealed a steroid profile estimated as normal with a testosterone (T)/DHT ratio of 9.5 initially misleading to the exclusion of 5α-reductase deficiency. However, mutation analysis of the SRD5A2 gene revealed a homozygote point mutation (Leu55Gln) confirming the diagnosis of 5α-reductase deficiency. A male phenotype was successfully achieved by hormone treatment with T and DHT after diagnosing 5α-reductase deficiency and a masculinization operation. As a side effect skeletal age accelerated temporarily. Conclusion: In individuals with predominantly female phenotype and suspected 5α-reductase deficiency, a T/DHT ratio during the neonatal period >8.5 might point to 5α-reductase deficiency. After confirmation of the diagnosis by molecular analysis of the SRD5A2 gene, a satisfactory change to a male phenotype can be achieved by hormone treatment preceding surgery.